Abstract 1470: Acute Muscle Stretch Induces a Time-dependent Decrease in Myocardial Stiffness: A Novel PKC-Mediated Effect.
Purpose: The acute response to myocardial stretch is classically described as inducing immediate and delayed increases in contractility, each one regulated by different molecular mechanisms. Despite the evidence that some of the latter mechanisms might also regulate the myocardial diastolic properties after acute muscle stretch, their roles remain to be clarified in this setting.
Methods: Rabbit papillary muscles (modified Krebs solution, 0.2Hz, 1.8mM Ca2+, 30°C) were acutely stretched from 92% Lmax to 100% Lmax (length at which maximal force is developed) in the absence (n=8) or presence of amiloride (a Na+/H+-exchanger inhibitor; n=6), chelerythrine (a selective protein kinase C inhibitor, PKC; n=7), L-nitro-arginine (a nitric oxide synthase inhibitor; n=8) or KT-5720 (a selective protein kinase A inhibitor; n=7). Immediate and delayed responses to muscle stretch were evaluated. Results presented as mean ± standard error (p<0.05).
Results: At baseline conditions, myocardial stretch promoted an immediate increase in contractility, inducing a 33.4±5.4% increase in Active Tension (AT), followed by a 10 minute elevation of 35.5±14.5% over the acute response, remaining then constant until the end of the protocol (60 minutes). While the delayed response was inhibited by amiloride and chelerythrine, none of these inhibitors affected the immediate increase in AT. On the other hand, after an initial and stretch-induced increase of myocardial Passive Tension (PT), this parameter showed a delayed and continuous decrease, reaching a maximum of 54.7±2.9% at 35 minutes, remaining then constant until the end of the experiment. This PT decrease was significantly attenuated by chelerythrine (−39.5±2.1%).
Conclusion: Myocardial stretch induces a delayed and significant decrease in cardiac muscle stiffness (PT decrease at constant muscle length), which is partially mediated by PKC. On the other hand, the delayed increase in contractility is PKC and Na+/H+-exchanger dependent. Therefore, the decrease in myocardial stiffness that follows muscle stretch allows the ventricle to increase its contractility after an elevation of end-diastolic volume with filling pressures more than 50% lower, thus decreasing the odds of pulmonary congestion.