Experiments with animals with various species-specific life span (rats, rabbits, cats, dogs) and different models (in situ heart, isolated perfused heart, isolated papillary muscle) have proved the reduction of functional capacity of the ageing heart. Diversely directional age-dependent shifts have been established involving myocardial Ca²⁺ transport system, i.e. an increase in the rate of Na⁺-Ca²⁺ exchange and passive Ca²⁺ transport across sarcolemma and a decrease in its Ca²⁺-binding capacity and a decrease in Ca²⁺ accumulation by sarcoplasmic reticulum and mitochondria (Ca²⁺ uptake). The experiments revealed a decrease in the Ca²⁺ ATPase myosin activity in the myocardium of aged animals and absence of age changes in the K⁺ ATPase activity. The findings obtained suggest that the development in the cardiac contractile function disorders in ageing largely depends on the age-related changes in the Ca²⁺ transport system.

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Experiments on rats and rabbits using models of arrhythmias induced by vasopressin, epinephrine, strophanthin, and CaCl₂ showed that antioxidants derived from 1,4-dihydropyridines, dibunol, and α-tocopherol possessed antiarrhythmic effects. Administration of these antioxidants decreased the occurrence of extrasystoles, disturbances of atrioventricular conductivity and ventricular fibrillation. These drugs also prevented changes in membrane phospholipid composition, inhibited activation of peroxidation, decreased phospholipase activity, prevented a decrease of Ca²⁺ ATPase and Ca²⁺ binding and uptake by sarcoplasmic reticulum, and increased sarcolemmal Na⁺, K⁺-ATPase, sarcoplasmic reticulum creatine phosphokinase.

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KEY WORDS: coronary vessels; adrenergic and cholinergic nervous stimulation.Disturbances of the coronary circulation arise most frequently in elderly and old people. Until recently, however, no special analysis has been undertaken of the character of regulation of coronary vascular tone during aging. Adrenergic and cholinergic influences, either of the direct nervous or mediator type, are known to lower coronary vascular tone and to increase the coronary blood flow [3-6, 9, ii, 12].Age differences in the response of the coronary vessels to adrenergic and cholinergic nervous stimulation and to administration of the mediator of the corresponding systems (catecholamines, acetylcholine) were studied in the investigation described below. EXPERIMENTAL METHODExperiments were carried out on adult (2-5 years) and old (12-17 years) mongrel dogs weighing 13-26 kg, under thiopental (30 mg/kg) anesthesia without thoracotomy and during natural breathing. Changes in the regional vascular resistance were judged from changes in perfusion pressure during perfusion of the hemodynamically isolated vascular region with a constant blood flow [8]. The left coronary artery was catheterized with a metal catheter [i0]. Parallel recordings were made of the pressure in the left ventricle and its first derivative, the systemic arterial pressure, and the resistance of vessels of the hind limb by means of a polygraph (Nihon Kohden, Japan). Postganglionic fibers of the stellate ganglion and the peipheral end of the divided vagus nerve were stimulated with square pulses of current from an ISE-01 stimulator through an isolating transformer. Noradrenalin, adrenalin, and acetylcholine over a wide range of doses (from 0.00001 to 5.0 ~g) were injected into the extracorporeal coronary blood flow. EXPERIMENTAL RESULTSIn the experiments of series I, threshold values of stimulation of postganglionic fibers of the stellate ganglion and the trunk of the right vagus nerve causing changes in coronary vascular tone in the experimental animals were determined. In all experiments both on adult and on old dogs, stimulation of these nerve fibers with a sufficiently strong current evoked coronary vasodilation. Meanwhile the threshold strength of stimulation causing changes in coronary vascular tone was higher in the old dogs. For instance, dilation of the coronary vessels in response to stimulation of postganglionic fibers of the stellate ganglion occurred in adult dogs when current with a voltage of 0.55 • 0.03 V was used, compared with 1.2• 0.02 V in old dogs. The threshold of the vagus nerve ~ffect on the coronary vessels was also raised in old age. For instance, coronary vasodilation developed in adult dogs when a current with a voltage of 0.4• 0.02 V was used, compared with 0.9• 0.03 V in old dogs (Fig. I). During stimulation of threshold strength a change in coronary vascular tone occurred without any change in the hemodynamics or cardiodynamics.