ABSTRACT
Effect of nifedipine post-treatment (100 micrograms/kg slow bolus followed by 3 micrograms/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (I) (20 min.) followed by 1 hr of reperfusion (R) was studied in pentobarbitone-anaesthetized open-chest coronary ligated dogs. In the control group, 1 hr of reperfusion failed to cause any significant recovery of the depressed LVdP/dtmax and that of the elevated LVEDP (LVdP/dtmax, pre-ischemic: 2720 +/- 90 mm Hg/sec., 20 min. of I: 2410 +/- 120 mm Hg/sec and 60 min. of R: 2210 +/- 130 mm Hg/sec. LVEDP, pre-ischemic: 5.25 +/- 0.2 mm Hg, 20 min. of I: 10.5 +/- 0.9 mm Hg and 60 min. of R: 7.5 +/- 0.5 mm Hg). However, 1 hr of reperfusion caused a significant recovery of ischemia-induced depletion of myocardial creatine phosphate (CP) content only, but not that of ATP. On post-treatment with nifedipine (i.e., infusion started just before reperfusion), there was a significant recovery in LVEDP (8.25 +/- 0.6 mm Hg after 20 min. of ischemia to 5.0 +/- 0.4 mm Hg after 1 hr of reperfusion) and there was no further deterioration in LVdP/dtmax, as observed in untreated dogs. More significantly, nifedipine caused a near normal recovery of both ATP and CP contents of the affected myocardium. Therefore, the present study shows that post-ischemic administration of nifedipine prevented reperfusion injury of the ischemic myocardium, as evidenced by both functional and metabolic recovery.
Subject(s)
Adenosine Triphosphate/metabolism , Animals , Dogs , Female , Male , Myocardial Reperfusion Injury/metabolism , Nifedipine/pharmacology , Phosphocreatine/metabolism , Ventricular Function, Left/drug effectsABSTRACT
Effect of verapamil post-treatment (0.2 mg/kg bolus, followed by 0.01 mg/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (20 min) followed by 1 hr of reperfusion was studied in open-chest pentobarbitone anaesthetized dogs. In control dogs 1 hr of reperfusion failed to cause any improvement of depressed myocardial contractility (LVdP/dtmax and LVEDP) caused by 20 min of ischemia, which confirmed the earlier reported phenomenon of 'Stunned Myocardium'. Myocardial ischemia caused a significant loss of high-energy phosphate (HEP) content of the affected myocardium (ATP decreased by 60% and CP decreased by 75% of non-ischemic level). Following 1 hr of reperfusion, myocardial ATP was not replenished, though creatine phosphate became near normal. When verapamil was administered just before reperfusion, it showed a profound beneficial effect on the incidence of fatal reperfusion arrhythmias. At the end of 1 hr of reperfusion in this group, the recovery of the myocardial contractility was incomplete, but a significant replenishment of the myocardial HEP content was observed. Thus verapamil post-treatment can prevent reperfusion-induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depressant effect.
Subject(s)
Adenosine Triphosphate/metabolism , Animals , Creatine Kinase/metabolism , Depression, Chemical , Dogs , Myocardial Contraction/drug effects , Myocardial Reperfusion Injury/physiopathology , Ventricular Fibrillation/prevention & control , Verapamil/pharmacologyABSTRACT
Biochemical alterations in the hearts of non-diabetic and 5 weeks of streptozotocin-induced diabetic rats following isoproterenol (ISO) administration were compared. Serum lactate dehydrogenase (LDH) and myocardial adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycogen were used as indices of myocardial injury. Hearts from diabetic rats (blood glucose greater than 350 mg/dl), before ISO administration, had normal lactate levels but significantly low high-energy phosphate (HEP) levels and high glycogen levels in comparison to non-diabetic rats. No difference was observed in serum LDH levels between these two groups. ISO administration to non-diabetic rats caused myocardial necrosis as evidenced by a significant depletion of myocardial glycogen and HEPs along with significant myocardial lactate accumulation and an increase in serum LDH. However, the hearts from diabetic rats failed to show any significant HEP depletion, accumulation of lactate and leakage of LDH into serum following ISO-administration, though myocardial glycogen level was significantly lowered. These observations, in conjunction with earlier reports, point to the hypothesis that, in diabetes, there are certain alterations in the sarcolemma which hamper the process by which ISO causes myocardial necrosis.