- Email: [email protected]
Effect of verapamil pretreatment on ischaemic and reperfused myocardium: A morphometric study
88 EFFECT OF MYOCARDIUM
VERAPAMIL PRETREATMENT ON : A MORPHOMETRIC STUDY.
ISCHAEMIC A.M. Slade
AND REPERFUSED and W.G. Nayler,
Cardiothoracic Institute, University of London, 2 Seoumont Street, London, WIN 2DX England. Thirty-six rabbits were treated subcutaneously twice daily for 45 days with either 2 mg/kg 0.9% NaC I, or 2 m&g racemate verapami I. Langendorff perfused hearts were divided into control, 90 min total ischaemia and 90 min total ischaemia with 15 min reperfusion. Multiple samples of perfusion fixed left ventricular myocardium were taken from six saline and six verapamil pretreated animals for each group and processed for electron microscopy. Micrographs were assessed for myocardial component volume using a point counting technique. Verapamil pretreatment caused an increased vascular volume in cantrols, with little alteration to myocyte organelle volume. However, the myocardial response to ischaemia was altered by verapamil pretreatment. A marked reduction of lipid droplet accumulation and no detectable decrease in transverse tubular volume was seen, and mitochondrial, nuclear and cytosolic swelling persisted. Myocardial response to reperfusion was also modified. Lipid Increased cytosolic space was prevented with no further nuclear swelling. droplets further decreased, vascular reduction was less marked and a reduction in myofibri liar volume was abolished. These resu Its showed that verapamil pretreatment provided ultrastructural protectian against the deleterious effects of ischaemia and reperfusion. (Supported by the Medical Research Council).
HAEMODYNAMIC AND METABOLIC EFFECTS OF INOSINE DURING ACUTE ISCHAEMIC LEFT VENTRICULAR FAILURE IN DOGS. O.A. Smiseth and O.D. Mjes. Institute of Medical Biology, University of Troms.0, Troms0, Norway. The present study was done to determine whether the positive inotropic and vasodilating nucleoside inosine might improve cardiac performance and metabolism during ischaemic left ventricular (LV) failure. LV failure was induced in 8 closed-chest pentobarbital anaesthetized dogs by injection of 50 urn plastic microspheres into the main left coronary artery. Intravenous infusion of inosine (3.87.5 mg/kg/min) effected an increase of LVdP/dt max from 2177& 241 to 2829? 290 mmHg/s (mean? SEM), and reductions of LV end-diastolic pressure from 26.9k1.6 to 18.5kl.l mmHg and of total peripheral resistance from 77+8 to 55% 5 mmHg . min/l. Cardiac output increased from 1.64tO.17 to 2.27?0.231/min and myocardial blood flow from 65+ 10 to 94? 16 ml/min/lOO g. Heart rate, aortic blood pressure and myocardial 02-consumption remained unaltered. Inosine effected reductions of arterial plasma concentrations of free fatty acids (FFA) and glucose from 310~ 20 to 140+ 20 pmol/l and from 6.29kO.14 to 4.79+ 0.34 mmol/l, respectively. Myocardial uptake of FFA decreased from 2.9kO.6 to 1.2kO.2 umol/min/lOO g, while myocardial glucose uptake showed a non-significant increase from 23.5+ 3.9 to 29.0? 5.7 pmol/min/ 100 g. Myocardial lactate uptake increased from 20.7+ 5.6 to 32.91r6.9 vmol/min/lOO g. In conclusion, inosine improved myocardial performance and metabolism in dogs with ischaemic LV failure.
VERAPAMIL PRETREATMENT ON : A MORPHOMETRIC STUDY.
ISCHAEMIC A.M. Slade
AND REPERFUSED and W.G. Nayler,
Cardiothoracic Institute, University of London, 2 Seoumont Street, London, WIN 2DX England. Thirty-six rabbits were treated subcutaneously twice daily for 45 days with either 2 mg/kg 0.9% NaC I, or 2 m&g racemate verapami I. Langendorff perfused hearts were divided into control, 90 min total ischaemia and 90 min total ischaemia with 15 min reperfusion. Multiple samples of perfusion fixed left ventricular myocardium were taken from six saline and six verapamil pretreated animals for each group and processed for electron microscopy. Micrographs were assessed for myocardial component volume using a point counting technique. Verapamil pretreatment caused an increased vascular volume in cantrols, with little alteration to myocyte organelle volume. However, the myocardial response to ischaemia was altered by verapamil pretreatment. A marked reduction of lipid droplet accumulation and no detectable decrease in transverse tubular volume was seen, and mitochondrial, nuclear and cytosolic swelling persisted. Myocardial response to reperfusion was also modified. Lipid Increased cytosolic space was prevented with no further nuclear swelling. droplets further decreased, vascular reduction was less marked and a reduction in myofibri liar volume was abolished. These resu Its showed that verapamil pretreatment provided ultrastructural protectian against the deleterious effects of ischaemia and reperfusion. (Supported by the Medical Research Council).
HAEMODYNAMIC AND METABOLIC EFFECTS OF INOSINE DURING ACUTE ISCHAEMIC LEFT VENTRICULAR FAILURE IN DOGS. O.A. Smiseth and O.D. Mjes. Institute of Medical Biology, University of Troms.0, Troms0, Norway. The present study was done to determine whether the positive inotropic and vasodilating nucleoside inosine might improve cardiac performance and metabolism during ischaemic left ventricular (LV) failure. LV failure was induced in 8 closed-chest pentobarbital anaesthetized dogs by injection of 50 urn plastic microspheres into the main left coronary artery. Intravenous infusion of inosine (3.87.5 mg/kg/min) effected an increase of LVdP/dt max from 2177& 241 to 2829? 290 mmHg/s (mean? SEM), and reductions of LV end-diastolic pressure from 26.9k1.6 to 18.5kl.l mmHg and of total peripheral resistance from 77+8 to 55% 5 mmHg . min/l. Cardiac output increased from 1.64tO.17 to 2.27?0.231/min and myocardial blood flow from 65+ 10 to 94? 16 ml/min/lOO g. Heart rate, aortic blood pressure and myocardial 02-consumption remained unaltered. Inosine effected reductions of arterial plasma concentrations of free fatty acids (FFA) and glucose from 310~ 20 to 140+ 20 pmol/l and from 6.29kO.14 to 4.79+ 0.34 mmol/l, respectively. Myocardial uptake of FFA decreased from 2.9kO.6 to 1.2kO.2 umol/min/lOO g, while myocardial glucose uptake showed a non-significant increase from 23.5+ 3.9 to 29.0? 5.7 pmol/min/ 100 g. Myocardial lactate uptake increased from 20.7+ 5.6 to 32.91r6.9 vmol/min/lOO g. In conclusion, inosine improved myocardial performance and metabolism in dogs with ischaemic LV failure.