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Cardiovascular Research 1998 38(1):149-157; doi:10.1016/S0008-6363(97)00322-2
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Copyright © 1998, European Society of Cardiology

Inotropic response of stunned hypertrophied myocardium: responsiveness of hypertrophied and normal postischemic isolated rat hearts to calcium and dopamine stimulation

Hans Martin Hoffmeister*, Markus Ströbele, Martin E Beyer, Silke Kazmaier, Marcus Fischer, Andrea Bäßler and Ludger Seipel

Medizinische Universitätsklinik, Abt. III; Eberhard-Karls-Universität Tübingen, Otfried-Müller-Straße 10, D-72076 Tübingen, Germany

* Corresponding author. Tel.: +49 (7071) 29-82088/82712; fax: +49 (7071) 29-2088.

Received 4 August 1997; accepted 3 December 1997


   Abstract
Top
 Abstract
1 Introduction
 2 Methods
 3 Results
 4 Discussion
 References
 
Objective: Severely hypertrophied myocardium was described to have a reduced tolerance towards ischemia. For non-hypertrophied hearts inconclusive findings on the Ca2+-responsiveness are reported. Information on sensitivity to reversible ischemia and on postischemic Ca2+-responsiveness of hearts with clinically common moderate hypertrophy is lacking. Thus, the responsiveness of hypertrophied and normal postischemic myocardium to positive inotropic stimulation should be investigated in the present study. Methods and results: Hearts from spontaneously hypertensive rats (SHR, 4 months old) with significant LV-hypertrophy (+50%) and hearts from normotensive 4 months old Wistar rats were investigated using an isovolumic beating isolated heart model (8 hearts/each of the 8 groups). Functional recovery after 30 min of no-flow ischemia was 78±1% and 77±3% of preischemic control data in hypertrophied and non-hypertrophied hearts assessed as developed left ventricular pressure (non-ischemic controls: 95±2% in hypertrophied and 93±3% in non-hypertrophied controls). Maximum short-term stimulation with Ca2+ revealed a decreased peak left ventricular pressure of 124±4% in hypertrophied and 120±5% in non-hypertrophied postischemic hearts, as compared with non-ischemic controls 138±3% and 157±5%, respectively (p<0.01). A maximum dose of dopamine stimulated hypertrophied and non-hypertrophied postischemic hearts comparable to Ca2+. Analysing the dose–response curve for Ca2+-stimulation, the sensitivity expressed as fraction of the maximum was identical in non-ischemic and postischemic myocardium of hypertrophied and non-hypertrophied ventricles in spite of the reduced peak values. Conclusion: The findings demonstrate that after moderate reversible ischemia the steady-state function is similarly decreased in hypertrophied and non-hypertrophied postischemic myocardium. The maximum response to Ca2+ is significantly reduced in both types of myocardium, while the Ca2+ sensitivity is unchanged. Identical results after maximum dopamine stimulation as after Ca2+ indicate that the releasibility of Ca2+ and the β-adrenoceptors are not the critical causes for the postischemic dysfunction in hypertrophied or non-hypertrophied myocardium.

KEYWORDS Postischemic myocardium; Hypertrophy; Inotropic stimulation; Dopamine


   1 Introduction
Top
 Abstract
 1 Introduction
2 Methods
 3 Results
 4 Discussion
 References
 
Reversibly injured postischemic myocardium is characterized by a sustained contractile dysfunction termed stunning [1]. Hypertrophied myocardium was described to be more susceptible to ischemic injury with respect to development of rigor [2], especially in postischemic failing hearts [3, 4]. A disturbed postischemic recovery of myocardial perfusion was reported [5, 6], especially in aged hearts [7]as a base of poorer recovery. The ischemic injury of the myocardium itself seems not to be more marked in hypertrophied hearts, as the reductions in adenine nucleotides [5], postischemic function [8]and infarct size [9]were similar in compensated hypertrophied myocardium as in normal hearts in most studies. In stunned myocardium a dysfunctional sarcoplasmatic reticulum was described in isolated postischemic hearts [10]and a reduction in maximum calcium-activated force was reported [11, 12]. Several studies reported a normal Ca2+-transient in postischemic myocardium [12–14]. A supposed [11]reduction in calcium sensitivity was not consistently found [12]. Therefore, a decreased myofilament Ca2+-responsiveness was proposed as a main reason for the reversible postischemic dysfunction [15]. In contrast to the in vitro studies, one in vivo study observed a normal contractile reserve in stunned regional canine myocardium using intracoronary Ca2+-infusion [16]. These results were challenged by a recent in vivo study on post-hibernation myocardium demonstrating a reduced contractile reserve upon intracoronary Ca2+ but a normal Ca2+-sensitivity [17]. The reduction in contractile reserve was described to be dependent on the degree of postischemic dysfunction and to be related only to more severe degrees of postischemic dysfunction [18]. In myocardial hypertrophy, which is discussed to have a reduced tolerance to myocardial ischemia [6, 19], no information is available about these issues.

In the present study the dose-dependent inotropic response of isolated postischemic hypertrophied hearts without irreversible tissue damage to dopamine or a Ca2+-stimulation was examined. The study aimed to investigate whether postischemic changes of maximum recruitable inotropic response and Ca2+-sensitivity are comparable in hypertrophied and non-hypertrophied myocardium.


   2 Methods
Top
 Abstract
 1 Introduction
 2 Methods
3 Results
 4 Discussion
 References
 
The study protocol of this investigation was proven by the authority of the district of Southern Württemberg and the animal care was in accordance with the guidelines of the American Physiological Society.

2.1 Isolated perfused rat heart
After anaesthesia with urethane (2.5 ml/kg of 50% solution intraperitoneally) the animals were artificially ventilated with room air (Starling pump, Braun, Melsungen, Germany) after introducing a small plastic tube into the trachea (tracheotomy). The chest was opened with a median sternotomy and 100 I.U. heparin were injected intravenously. After preparation the heart and the ascending aorta were excised and quickly immersed in ice cold saline. Adjacent tissue was rapidly trimmed away. The aorta was mounted on a steel cannula and retrograde perfusion was initiated. The perfusion was performed using a modified non-recirculating Langendorff apparatus. The perfusion pressure was set 100 cm H2O, which is within the autoregulation range of normal and hypertrophied rat hearts. In the strains examined in this study this pressure results in a coronary flow of 13.5±1 ml/min/g in the hypertrophied left ventricles and in a flow of 14.4±1 ml/min/g in the non-hypertrophied left ventricles.

The hearts were perfused with a Krebs–Henseleit buffer consisting of NaCl 115 mmol/l, NaHCO3 25.0 mmol/l, KCl 4.0 mmol/l, KH2PO4 0.9 mmol/l, CaCl2 2.6 mmol/l, MgSO4 1.1 mmol/l and glucose 5.5 mmol/l. The perfusate was warmed to 37°C and gassed with 95% O2/5% CO2. A fluid-filled latex balloon was connected via a short plastic tube to a Statham P23 Db transducer (Gould Inc., Oxnard, CA, USA) and was introduced via the mitral valve into the left ventricular cavity. The pressure signal was amplified and differentiated (dp/dt) using a physiological data recorder and monitored on a strip chart recorder (Hellige B78-18802, Freiburg, Germany). The hearts were not paced in this preparation. From the hemodynamic recordings the left ventricular developed pressure, dp/dtmax and dp/dtmin, heart rate and the double product (developed pressurexheart rate) were derived. After instrumentation the hearts were placed in a temperature-regulated glass jacket in order to maintain a stable temperature.

2.2 Animals
Hearts from male rats with free access to water and standard laboratory animal feed (Altromin GmbH, Lage-Lippe, Germany) were used. Young adult spontaneously hypertensive rats (SHR; 4 months old) (SHR/NCrlBR; Charles River GmbH, Sulzfeld, Germany) had a significant left ventricular hypertrophy with an increase of the left ventricular to body weight ratio to 150% compared with age-matched normotensive rats (left ventricular/body weight ratio of SHRs: 3.15±0.05 vs. 2.08±0.05 g/kg in non-hypertrophied hearts (p<0.01). Left ventricular weight was 1.10±0.03 g in SHR and 0.84±0.1 g in Wistar rats (p<0.01). At this stage of hypertrophy cardiac function is fully compensated [7]. As non-hypertrophied controls the hearts from 4 months old normotensive Wistar rats ((Chbb: THOM/SPF) Thomae GmbH, Biberach, Germany) were used.

2.3 Protocol
After preparation the hearts were allowed to stabilize in the unloading beating state for 10 min. Thereafter, the intraventricular balloon was inflated and adjusted by a high-precision syringe system to a volume corresponding to an end-diastolic left ventricular pressure of 6 mmHg. The balloon volume was constant over time in the different groups. This left ventricular filling was chosen, since in isovolumic registrations in these hearts the preload/response curve is flat and this preload results in about 90% of the maximum isovolumic unstimulated pressure in both types of hearts. After this initial stabilization period the preischemic control data were obtained. Over a period of 10 min the hearts then stabilized again as isovolumically contracting hearts. Thereafter 30 min of no-flow ischemia with unloaded balloon was performed. In the control group the hearts beat meanwhile with retrograde perfusion and deflated balloon. After ischemia the hearts had a 15 min period of unloaded reperfusion and were then switched to the isovolumic beating mode. Afterwards the hearts were kept in the isovolumic beating mode until a total time of 50 min post ischemia. Stability of the postischemic function was controlled by hemodynamic measurements 20 and 50 min after ischemia. Fifty minutes after ischemia stimulation by 8 stepwise increasing doses of Ca2+-gluconate (Braun, Melsungen, Germany) via a side branch of the aortic cannula using a precision pump system was started. Each dose (starting with 2 µmol/min and doubling up to 250 µmol/min) was infused for 3 min (maximum effect reached about at the second minute) and then followed by a 5 minute wash-out before the next dose was given. The highest developed pressure during stimulation was termed maximum response. An identical protocol was used in those ventricles, which were stimulated with dopamine solution (Nattermann and Cie GmbH, Köln, Germany) with doses from 0.07 mg/min to 10 mg/min in 8 steps. 10 to 20% of the hearts did not tolerate the highest stimulation dose (independently from the group) and experienced ventricular fibrillation and asystole. From the latter hearts the highest obtained value was taken as maximum response. A total of 8 groups was investigated, each with 8 hearts: Four groups without ischemia and either Ca2+ or dopamine stimulation with hypertrophied hearts or with non-hypertrophied hearts and four postischemic groups with either Ca2+ or dopamine stimulation in both types of hearts.

2.4 Statistical evaluation
All hemodynamic data were given as means±SEM. For comparison between hypertrophied and non-hypertrophied hearts the data after ischemia were normalized to the individual preischemic control measurements. For statistical analysis storage on an EXCEL data system was used and statistical evaluation was performed using the statistical package JMP [20]. Data were analyzed using an overall MANOVA. Follow-up data were evaluated using an ANOVA with correction for repetitive testing (Bonferroni). For evaluation of contractile reserve a three way analysis of variance and a Tuckey–Kramer HSD test were applied. A p<0.05 was set as level of significance.


   3 Results
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
4 Discussion
 References
 
3.1 Steady-state function
The preischemic data of the hypertrophied hearts and of the non-hypertrophied hearts were comparable within the two groups (Table 1). The stability of the preparation is demonstrated by the data of the control hearts at the end of the experiments (Table 2). The developed left ventricular pressure, dp/dtmax, dp/dtmin, double product and coronary flow of the hearts from spontaneously hypertensive rats were higher (p<0.01) compared with the measures from normotensive rats. 30 min of ischemia resulted in both groups of hearts in a stable postischemic state with identical hemodynamic data 20 and 50 min after ischemia (Table 2). In the present model of a moderate ischemic injury the reduction in developed left ventricular pressure in hypertrophied (–40 mmHg=–22%) and non-hypertrophied (–31 mmHg=–23%) ventricles at the end of the 50 min reperfusion was identical (Table 3), while at 20 min reperfusion the developed left ventricular pressure was slightly more reduced (p<0.05) in hypertrophied hearts. Reduction in dp/dtmax and in the relaxation index dp/dtmin was also comparable in hypertrophied and non-hypertrophied left ventricles (Table 2). Since the heart rate of the spontaneously beating hearts was not significantly altered in the postischemic state compared to preischemic values, the reduction in the double product was in parallel to the reduction in the developed left ventricular pressure in hearts from normal and hypertensive rats (Table 2).


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  		Table 1 Initial hemodynamic data of all groups for comparison, indicating the difference between hypertrophied hearts from spontaneously hypertensive rats and non-hypertrophied myocardium of normotensive rats. Except heart rate and weight-related coronary flow all measures were higher (p<0.01 ANOVA; cumulative test of Wistar vs. SH-rats) in spontaneously hypertensive rats. All data are baseline measurements before ischemia and before infusion of the respective stimulus

 

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  		Table 2 Steady-state hemodynamic data at 20 min and 50 min reperfusion (rep.) in postischemic hypertrophied and non-hypertrophied myocardium in comparison to the respective non-ischemic control group before start of the stimulation with Ca2+ or dopamine. Reductions in LVP, dp/dtmax, dp/dtmin and double product were significant (p<0.01 ANOVA) for each species (cumulative test of postischemic Wistar or SH-rats vs. resp. controls), while HR and CF were not significantly altered.

 

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  		Table 3 Steady-state hemodynamic data at the end of the reperfusion period [=50 min reperfusion (rep.)] before start of the Ca2+ or dopamine stimulation. Data in % of the preischemic measurement for comparison between hypertrophied and non-hypertrophied hearts. All postischemic data were significantly reduced in both species (p<0.01 ANOVA; cumulative test of postischemic Wistar or SH-rats vs. resp. controls) except HR and CF. All inter-species differences (Wistar vs. SHR) were n.s.

 
3.2 Maximum contractile response
The maximum inotropic response in normal hearts was comparable with Ca2+(157±5%) and dopamine (165±7%). The mean of the maximum developed left ventricular pressure from each left ventricle is given in Fig. 1, this maximum was obtained in most hearts from the third or second highest dose of the range tested. Comparable data were obtained in the control hearts for dp/dtmax with a maximum increase to 184±7% after Ca2+ and 239±16% after dopamine. dp/dtmax data were always higher after dopamine compared with the Ca2+-stimulation (p<0.01) as dopamine additionally increased the heart rate for a mean of 40% in hypertrophied or non-hypertrophied hearts independently whether they were in a control or postischemic state.


Figure 1
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  		Fig. 1 Comparison of the maximum inotropic response assessed as developed left ventricular pressure (LVP) and dp/dtmax of postischemic and control (non-ischemic) myocardium after Ca2+ or dopamine stimulation. Identical results with a significant reduction of the contractile reserve in postischemic myocardium (identically for Ca2+ and dopamine) were obtained in hypertrophied (a) and non-hypertrophied (b) myocardium (*=p<0.05; **=p<0.01) using a three-way ANOVA for the comparison of the respective postischemic and non-ischemic groups. For hypertrophied vs. non-hypertrophied: n.s.

 
The contractile reserve in postischemic hearts was significantly lower compared with non-ischemic normal left ventricles (p<0.01; Fig. 1). Maximum developed left ventricular pressure was 37% lower after Ca2+ and 52% lower after dopamine stimulation compared with non-ischemic ventricles. dp/dtmax was also considerably reduced (p<0.01) independently from the mode of stimulation.

The maximum stimulated contractile response in non-ischemic hypertrophied hearts was an increase of the developed left ventricular pressure to 138±3% after Ca2+ and to 139±5% after dopamine. dp/dtmax was also increased with Ca2+ and more markedly with dopamine stimulation (p<0.01; Fig. 1). Compensated hypertrophied left ventricles of young adult spontaneously hypertensive rats had no evidence for an increased susceptibility to ischemia with a reduction in postischemic steady-state function similar to that of hearts from normotensive rats (Table 2). Maximum contractile response of hypertrophied postischemic hearts was comparably decreased after Ca2+ and after dopamine as judged by the maximum developed left ventricular pressure (p<0.01; Fig. 1). Similar results were obtained for dp/dtmax after Ca2+ and after dopamine (p<0.01; Fig. 1).

Stimulation with Ca2+ and with dopamine had a comparable maximum effect in hypertrophied and in non-hypertrophied left ventricles related to the control measurements. The postischemic reduction in maximum inotropic response was similar in compensated hypertrophied and non-hypertrophied left ventricles (Fig. 1). Thus no difference between the two types of postischemic myocardium in normalized steady-state function nor in maximum response related to controls was found.

3.3 Sensitivity to Ca2+-stimulation
For evaluation of myocardial sensitivity to Ca2+ the increase of left ventricular pressure or dp/dtmax after each dose was expressed as a fraction of the maximum response and plotted versus a logarithmic scale of the Ca2+-doses (Fig. 2Fig. 3). For non-hypertrophied postischemic and non-ischemic hearts the dose–response relations for developed left ventricular pressure (non-ischemic: y=0.65logx–0.21, r=0.97; postischemic: y=0.64logx–0.13, r=0.93) and dp/dtmax (non-ischemic: y=0.68logx–0.27, r=0.92; postischemic: y=0.68logx–0.20, r=0.84) were identical, indicating an unchanged sensitivity to Ca2+-stimulation of the contractile apparatus of postischemic myocardium. In hypertrophied left ventricles both for developed left ventricular pressure and for dp/dtmax a response curve comparable as in non-hypertrophied hearts was obtained (Figs. 2 and 3Go). As for normotensive hearts, the lines of the dose response were not different between non-ischemic and postischemic hypertrophied ventricles for developed left ventricular pressure (non-ischemic: y=0.56logx–0.17, r=0.87; postischemic: y=0.61logx–0.15, r=0.92) and dp/dtmax (non-ischemic: y=0.57logx–0.20, r=0.85; postischemic: y=0.62logx–0.19, r=0.90) as an indicator of a comparable sensitivity to Ca2+-stimulation.


Figure 2
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  		Fig. 2 Plot of the dose–response curve after Ca2+-stimulation of hypertrophied (a) and non-hypertrophied (b) non-ischemic and postischemic myocardium at the end of the reperfusion period, indicating comparable response to Ca2+. Ca2+ doses at the abscissa in a log scale. Left ventricular pressure expressed as a fraction of the maximum response (=1) on the ordinate.

 

Figure 3
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  		Fig. 3 Plot of the dose–response curve after Ca2+-stimulation of hypertrophied (a) and non-hypertrophied (b) non-ischemic and postischemic myocardium at the end of the reperfusion period, indicating comparable response to Ca2+. Ca2+ doses at the abscissa in a log scale. dp/dtmax expressed as a fraction of the maximum response (=1) on the ordinate.

 

   4 Discussion
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
References
 
The present study was undertaken to examine the inotropic response of postischemic hypertrophied myocardium. Stimulation revealed a reduced maximum inotropic response in postischemic hypertrophied and non-hypertrophied myocardium, whereas a decreased sensitivity to Ca2+-stimulation was not detectable.

4.1 Tolerance of moderate left ventricular hypertrophy to ischemia
4.1.1 Limitations and strengths of the model
This experimental set-up produces a stable postischemic dysfunction with a reduction in indices of function to about 70% and a decrease of adenine nucleotide levels to about 60% without any histological or biochemical evidence for irreversible ischemic injury [18]. As outlined by Bolli [21]buffer-perfused systems cannot cover all facets of stunning, since e.g. recovery cannot be proven due to the limited stability in the long term. Compared with regional ischemia in vivo additional influences from corpuscular and non-corpuscular elements of the blood as well as possible effects of regional interactions and collateralization, which cannot be definitively ruled out in vivo, are not a problem in global ischemia in vitro. The stability of isolated hearts is known to be limited and edema formation may influence the findings. Measurements of dry weight/wet weight ratios in a pre-study using the identical experimental set-up as in the present study have shown that only a moderate and comparable edema formation occurs during the 1.5 h of cristalloid perfusion without significant difference between hypertrophied or non-hypertrophied hearts with or without previous ischemia.

A large number of models are used to induce left ventricular hypertrophy. We aimed to have a model with a well documented hypertrophy, which was already used to study effects of ischemia [19], with a known reduction in high energy phosphates. The degree of hypertrophy was chosen to be close to a clinically typical increase in left ventricular mass without occurrence of cardiac failure, which occurs in these rats at an age of 18–24 months [7]. Stimulation in postischemic models is always a compromise between more or less physiological conditions [17]. In contrast to in vivo models, Ca2+-dosing in the present model could be exactly titrated and pressure-derived indices as most reliable measures of contractile performance in the intact coronary perfused heart could be obtained. However, direct comparison of in vitro and regional in vivo data is limited, as regional interaction may significantly influence the results.

4.2 Susceptibility to ischemia
Several reports have dealt with the reduced tolerance of hypertrophied myocardium towards ischemia. A reduced tolerance was mainly observed for the onset of contracture or irreversible tissue damage [2, 22]. Most experimental studies, which report an increased susceptibility, are based on decompensated or aged myocardium [4, 7]. For moderately hypertrophied non-failing myocardium a reduced tolerance towards ischemia was described to be dependent on the reperfusion pressure [5, 6], but reperfusion of hypertrophied hearts with relative low pressure as in the above cited study might favour development of focal irreversible damage limiting a comparison with normal hearts. Thus the reported reduced tolerance might be a circulatory and not a myocardial problem [5, 6]. This assumption would be in accordance with the findings that the decrease of the adenine nucleotide content, which is regarded as an indicator of myocardial ischemic damage [23], was the same in hypertrophied and non-hypertrophied myocardium [5]. Comparable results were reported in a preliminary study from our laboratory [24]using a model similar as in the present study, in which the postischemic steady-state function was identically reduced after a moderate ischemic injury in hypertrophied and non-hypertrophied myocardium. After reperfusion with sufficient pressure all determined measures of systolic function indicated a comparable severity of stunning. Comparable findings were reported from a classical coronary artery occlusion experiment regarding comparison of infarct sizes [9]. Despite differences in the increase in coronary flow during pharmacological stress the absence of a reduced tolerance towards ischemia in moderate ischemia was reported by Massie et al. [25]. In this study as in the present study a moderate left ventricular hypertrophy was examined, which is clinically the most relevant form. In this condition there is no evidence from the literature and from the present study for an increased prolonged susceptibility towards ischemia judged from postischemic steady-state data.

4.3 Inotropic response of stunned hypertrophied myocardium
Inotropic stimulation of postischemic myocardium is feasible, but the extent of the response (normal or reduced) is discussed controversial. A normal or near normal response was described by some groups [16, 26, 27], especially in classically stunned myocardium after release of a transient coronary occlusion, while in postischemic in vitro experiments a reduced maximum response was frequently observed [11, 12]. A gradual reduction in the maximum response to catecholamine stimulation was observed depending on the severity of the previous ischemic injury [18]. In that study the reduction in maximum response was not as obvious as the decreased steady-state function after only moderate ischemia: this observation might explain why depending on the model in some studies on stunning the maximum contractile response was still regarded to be normal, whereas in other studies a significant decrease was found. The latter result was also reported from an investigation of post-hibernation myocardium [17]. However, data on stimulation of hypertrophied myocardium are lacking.

Compared with non-ischemic myocardium this maximum inotropic response is significantly reduced for non-failing hypertrophied and non-hypertrophied postischemic myocardium. The reversible prolonged postischemic dysfunction was discussed to be related to a dysfunctional sarcoplasmatic reticulum [10]. Several steps could be involved: the Ca2+-transient, the myofilamental Ca2+-sensitivity and possibly the maximum response to Ca2+ [13]. The Ca2+-transient was reported to be normal in most studies [12–14], whereas controversial data exist on the Ca2+-sensitivity [11, 17]. It might be assumed that the sensitivity might be reduced to explain the decreased function in the presence of normal Ca2+-transients. Since our present data in accordance to the findings of Heusch et al. [17]in hibernating and post hibernation myocardium indicate a normal sensitivity to Ca2+, this explanation seems to be unlikely. Therefore, the reduction in maximum force and in the force per given Ca2+ remains as explanation for the dysfunction both for hypertrophied and non-hypertrophied myocardium. Other causes such as an insufficient energy delivery can be ruled out, as ATP repletion had no effect on postischemic dysfunction [28]and prolonged positive inotropic stimulation to a normal level of function does not cause an energetic exhaustion and a consecutive dysfunction in postischemic myocardium [18]. Furthermore, a beneficial effect of catecholamines on the energetics in postischemic myocardium was described [29, 30].

A sufficient availability of released Ca2+ is proven by the identical maxima after Ca2+- and dopamine-stimulation: Even without supplementation of Ca2+ the maximal possible response can be achieved by dopamine in postischemic hypertrophied as well as in non-hypertrophied myocardium. A dysfunction of the sarcoplasmatic reticulum is therefore very unlikely. Dopamine stimulation also indicated that alterations in the signal transduction are not responsible for the reduced postischemic maxima, as the maximum response was obtained in hypertrophied and non-hypertrophied myocardium at the identical doses in postischemic and non-ischemic hearts. In accordance to our findings Schulz et al. [31]could not demonstrate considerable alterations in adrenergic receptors in hypoperfused myocardium.

Ca2+-responsiveness of postischemic vs. non-ischemic hypertrophied myocardium was not examined until now. The findings of this study demonstrate that postischemic hypertrophied myocardium responds identically as non-hypertrophied myocardium to an inotropic challenge. This means that a dysfunction of the sarcoplasmatic reticulum is not the reason for the postischemic dysfunction. This observation stems from hearts with moderate hypertrophy without signs of decompensation; therefore it cannot be excluded that it is not valid for very severely hypertrophied or failing hypertrophied hearts. In both investigated types of heart muscle the maximum postischemic response is limited to a comparable extent in relation to the non-ischemic response. The maximum recruitable contractile reserve after Ca2+- and dopamine stimulation is identical indicating a sufficient availability of releasable Ca2+ and the absence of major disorders of the catecholamine-mediated inotropic activation. Prior studies with non-hypertrophied hearts on this issue did not investigate different stimuli in parallel. According to the present data the Ca2+-sensitivity appears to be unaltered in both hypertrophied and non-hypertrophied postischemic myocardium. The findings of our study imply that at least for moderately hypertrophied hearts as present in the majority of patients with arterial hypertension tolerance to ischemia is not limited and therefore hypertrophy should not result in an increased risk in ischemia associated procedures.

Time for primary review 39 days.


   References
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 References
 

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