Effect of inosine on contractile force and high-energy phosphates in ischemic hearts.
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Adenosine Triphosphate↗
Biomedical subjects
J X Thomas
Publications and source records attributed to J X Thomas.
The effect of chronic cardiac denervation on infarct size following acute coronary occlusion.
The effect of acute coronary ligation on infarct size was studied in (1) ten acute control dogs, which were non-denervated, (2) in six acutely denervated dogs in which the heart was denervated immediately prior to coronary ligation and in which intra-cardiac reflexes were pharmacologically blocked, (3) in seven chronically denervated dogs in which intrapericardial nerves were cut 2 weeks prior to ligation, and (4) in four dogs which were sham-operated 2 weeks prior to ligation. Infarct size was determined using a nitro blue tetrazolium stain for dehydrogenase activity. Infarct sizes in acute controls, acutely denervated, chronically denervated, and sham-operated hearts were 20.1, 15.0, 3.8, and 21.0 per cent of left ventricular weight, respectively. Infarct sizes in acutely and chronically denervated hearts were significantly less than in acute controls (P less than 0.05). In further studies the fluorescent stain thioflavin S was used to demonstrate that perfusion of myocardium distal to the ligation was substantially greater in chronically denervated hearts than in acute controls.
Acute Disease↗
Positive inotropic response to inosine in the in situ canine heart.
Effects of inosine on left ventricular contractile force, circumflex blood flow, heart rate, and arterial pressure were investigated in mongrel dogs. Infusion of 50 ml of 10, 25, or 50 mM inosine into the right atrium over 5 min produced arterial blood inosine concentrations of 20-120 microM. Infusion of inosine concentrations of 10 mM or greater produced statistically significant increases in contractile force and circumflex blood flow (P less than 0.05). The increases in contractile force and circumflex blood flow caused by 50 inosine were approximately 40% and 110%, respectively. No statistically significant increases in heart rate or arterial pressure were observed during infusion of inosine at any concentration. Administration of propranolol (2 mg/kg) in no way altered the effects of inosine on contractile force or circumflex blood flow. Thus, the present study suggests that inosine in concentrations which may be produced in the myocardium during stressful conditions causes a substantial effect on the inotropic state of the heart and that the effects of inosine are not mediated through adrenergic mechanisms.
Animals↗
Acute changes in high energy phosphates, nucleotide derivatives, and contractile force in ischaemic and nonischaemic canine myocardium following coronary occlusion.
Studies of ischaemic myocardium following occlusion of coronary arterial branches revealed a substantial decline in creatine phosphate, adenosine triphosphate, and total adenine nucleotide contents over 40 min. Contents of nucleotide breakdown derivatives increased significantly but transiently. Contractile force declined rapidly and stabilized at a low level. In nonischaemic muscle following occlusion creatine phosphate, adenosine triphosphate, and total nucleotide contents declined rapidly, although not to the degree seen in ischaemic muscle. Contents of derivatives increased only slightly. Contractile force increased.
Adenine Nucleotides↗
Effect of ischemia and infarction on regional content of adenine nucleotides and derivatives in canine left ventricle.
Samples of myocardium from four areas of ischemic and infarcted canine ventricle were examined over a 20-day period for content of the three adenine nucleotides as well as inosine, hypoxanthine, adenosine, and inosine monophosphate. The adenosine triphosphate (ATP) content of central and peripheral areas within the infarct fell to 11% and 8% of control, respectively, 1 day after coronary occlusion. The total adenine nucleotide (TAN) content in these areas fell to 17% of control and showed no significant recovery during the period of study. In the functional myocardium immediately surrounding the infarct the ATP content was depressed to 58% control after 1 day, and the TAN content was also depressed. In the healthy myocardium near the apex, the ATP content was significantly depressed only at the 3-day sample period. Adenine nucleotide derivatives were detected only at 30 min in the central ischemic area. The absence of the nucleoside and nucleobase compounds formed during adenine nucleotide degradation is attributed to their high membrane diffusibility. Loss of these compounds is considered a contributing factor in the prolonged depression of adenine nucleotide content in both ischemic and non-ischemic regions.
Adenine Nucleotides↗
Effects of cardiac sympathetic nerve stimulation during adrenergic blockade on infarct size in anesthetized dogs.
beta-Adrenergic blockade has been shown to limit myocardial infarct size (IS) in anesthetized dogs. The objective of the present study was to determine whether sympathetic activation in the presence of beta-adrenergic blockade would alter IS. Chloralose-anesthetized dogs were divided into five groups. All hearts were neurally decentralized and paced at 150 beats/min. The circumflex coronary artery was ligated distal to the first major branch. Group 1 (n = 5) had no treatment. Group 2 (n = 6) received timolol (0.2 mg/kg) intravenously before and throughout occlusion. Group 3 (n = 7) underwent left stellate stimulation (LSS; 8 Hz, 5 ms, 7-10 V) immediately following coronary artery occlusion and for the duration of occlusion. Group 4 (n = 5) received timolol in addition to LSS. Group 5 animals (n = 6) received prazosin (0.5 mg/kg i.v.) and timolol before circumflex occlusion and LSS following coronary artery occlusion. After 6 h, Evans blue dye was injected into the left atrium while the circumflex artery distal to the ligation was simultaneously perfused with saline. Hearts were rapidly excised, and the left ventricle was sliced and photographed. IS was determined and expressed as a percentage of the area at risk by planimetry. The following mean +/- SEM values were measured: Group 1, 23.5 +/- 5.3; Group 2, 34.2 +/- 1.4; Group 3, 31.4 +/- 7.8; Group 4, 59.3 +/- 3.9; and Group 5, 25.6 +/- 5.3%. Significant differences were found between Group 4 and all other groups (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗