Biomedical subjects

R Ferrari

Publications and source records attributed to R Ferrari.

At least 19 recordsLinked to original sources

PubMed1992

Effect of prolonged treatment with propionyl-L-carnitine on erucic acid-induced myocardial dysfunction in rats.

The aim of this study was to evaluate the ability of propionyl-L-carnitine to prevent cardiac damage induced by erucic acid. Rats were fed for 10 days with normal or 10% erucic acid-enriched diets with or without propionyl-L-carnitine intraperitoneally injected, (1 mM/kg daily, for 10 days). The erucic acid diet produced increases in triglycerides (from 5.6 to 12.4 mg/gww, P less than 0.01), and free fatty acids (from 2.0 to 5.1 mg/gww, P less than 0.01), but no changes in phospholipids. When the hearts were perfused aerobically with an isovolumic preparation there was no difference in mechanical activity. On the contrary, when pressure-volume curves were determined, the pressure developed by hearts from the erucic acid-treated rats were reduced. Independent of diet, propionyl-L-carnitine treatment always produced positive inotropy. This was concomitant with improved mitochondrial respiration (RCI 5.1 vs 9.3, P less than 0.01), higher tissue ATP content (10.3 vs 18.4 mumol/gdw P less than 0.01) and reduction of triglycerides (12.4 vs 8.0 mg/gww, P less than 0.01). These data suggest that propionyl-L-carnitine, when given chronically, is able to prevent erucic acid-induced cardiotoxicity, probably by reducing triglyceride accumulation and improving energy metabolism.

Adenosine Triphosphate↗

PubMed1992

Effects of calcium antagonists on glycolysis of rat brain synaptosomes.

The effects of calcium antagonists nimodipine, nicardipine and flunarizine on lactate production and specific activities of some enzymes regulating glycolytic flux have been evaluated in synaptosomes isolated from rat whole brain and submitted to in vitro chemical hypoxia induced by rotenone, an inhibitor of mitochondrial respiration. The following enzymes have been tested; hexokinase (ATP: D-hexose-6-phosphotransferase, EC2.7.1.1), phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40). The results show that rotenone increases by about eight times the production of lactate; nicardipine and nimodipine, starting from a concentration of 10(-4) M, were able to counteract the rotenone-induced stimulation of glycolysis, but flunarizine was without effect. The dihydropyridines but not flunarizine decreased the maximum activity of phosphofructokinase. This effect was already detectable at a concentration of 10(-5) M. Neither hexokinase nor pyruvate kinase were affected by any of the drugs studied.

Animals↗

PubMed1992

Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease.

Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients with Parkinson's disease. In comparison with age-matched controls, no consistent abnormality could be discerned in complex I, complex II-III, or complex IV oxygen consumption, or in the enzyme activity of these respiratory chain complexes. Neither chronic therapy with levodopa/carbidopa alone nor in combination with deprenyl significantly affected any measure of mitochondrial respiratory function. There was no discernible relationship between patient age or disease severity and any parameter of mitochondrial respiration. Moreover, blood lactate levels following glucose loading were not different in patients and controls. These results fail to support the occurrence of a generalized defect in any mitochondrial respiratory function in Parkinson's disease.

Age Factors↗

PubMed1992

Role of timing of administration in the cardioprotective effect of fructose-1,6-bisphosphate.

We administered fructose-1,6-bisphosphate (FDP), 1 mM, to isolated and perfused rabbit hearts submitted, after 90 minutes of equilibration, to an ischemic period (60 minutes at a coronary flow of 0.17 ml/min/g), followed by a period of reperfusion (30 minutes at a coronary flow of 3.6 ml/min/g). FDP was delivered at different times following the experimental protocol: 60 minutes before ischemia and for the entire experiment; 60 minutes before and during ischemia, but not at reperfusion; at the onset of ischemia and during reperfusion; and only during reperfusion. The FDP cardioprotective effect was evaluated in terms of recovery of left ventricular pressure developed during reperfusion, creatine phosphokinase (CPK) and noradrenaline release, mitochondrial function (expressed as yield, RCI, QO2, ADP/O), ATP and creatine phosphate (CP) tissue contents, calcium homeostasis, and by measuring oxidative stress in terms of reduced and oxidized glutathione release and tissue contents. Our data show that the cytoprotective action of FDP is closely related to the time of administration. Optimal myocardial preservation was achieved when it was present prior to ischemia and during reperfusion. When given at the time of ischemia or only on reperfusion, FDP does not exert cardioprotection. The data suggest that the FDP cardioprotective effect is related to improvement of energy metabolism.

Adenosine Triphosphate↗

PubMed1992

Hibernating myocardium in patients with coronary artery disease: identification and clinical importance.

The term hibernating myocardium describes a particular outcome of myocardial ischemia in which myocytes show a chronically depressed contractile ability but remain viable. Revascularization of hibernating tissue causes a recovery of mechanical function that correlates with long-term survival. Therefore it is important clinically to distinguish hibernating from infarcted myocardium, since asynergies due to hibernation will improve on reperfusion, whilst those due to infarct will not. One suggested technique to identify hibernating myocardium is to stimulate the myocytes acutely, but briefly, by administration of inotropic agents while monitoring contractile function by echocardiography. We report our experience on the use of low dosages of dobutamine. Myocardial viability was validated by measuring the recovery in contraction of the akinetic areas after coronary artery bypass surgery by means of intraoperative epicardial echocardiography. The test has a sensitivity of 93% and a specificity of 78%. It is useful for identification of viable myocardium and also for quantification of intraoperative risk in individual patients. Limitations of this test are related to the presence of downregulation of beta receptors and to the impossibility of differentiating hibernating from stunned myocardium. Another useful technique of identifying hibernating myocardium is the use of radionuclear markers for viability. In our experience the two most important tests are (1) rest-redistribution imaging of thallium 201 (which has a high sensitivity of 93% but a low specificity of 44%) and (2) 99mTc-Sestamibi imaging, which provides information on both perfusion and function with a single injection. This latter technique allows differentiation between stunning and hibernating on the basis of coronary flow which is preserved in stunning and reduced in hibernation.

Cell Survival↗

PubMed1992

Effects of the novel calcium channel blocker, anipamil, on the isolated rabbit heart. Comparison with verapamil and gallopamil.

The calcium channel blocking activity of the novel phenylalkylamine derivative, anipamil, was tested on the isolated rabbit heart, in comparison with verapamil and gallopamil. Anipamil and the other calcium channel blockers lower left ventricular pressure in the same concentration range (10(-8)-10(-4) mol/l). The negative inotropic effect of anipamil is only partially reversed (nearly 65%) by rising calcium concentration in the perfusion fluid, whilst a complete recovery is observed for verapamil and gallopamil. The negative inotropic effect of anipamil is of rapid onset but long lasting, being still present 12 h after washout. On the contrary, that of gallopamil or verapamil completely disappears within 3 h of washout. Verapamil and gallopamil (10(-8)-10(-4) mol/l) depress spontaneous heart rate up to asystolia and abolish the vasopressin- and Bay K 8644-induced coronary spasm. Anipamil, on the contrary, does not modify coronary spasm elicited by both stimulants and spontaneous heart rate up to 10(-4) mol/l. These observations suggest that anipamil, in the isolated rabbit heart, possesses a peculiar pharmacological profile, since its calcium channel blocking activity is confined to the myocardial muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1992

Lipid peroxidation during myocardial reperfusion.

Reperfusion of heart muscle after prolonged ischaemia is associated with metabolic and functional abnormalities and eventual cell death. Free radical induced lipid peroxidation of cell membranes is thought to be a major mechanism in the evolution of reperfusion damage. The evidences in support for this kind of damage are based on tissue malondialdehyde quantitation by the thiobarbituric acid test (TBA-test). In an attempt to verify this topic we have subjected isolated and Langendorff perfused rabbit hearts to a period of 60 minutes of severe ischaemia plus 30 minutes of reperfusion. At appropriate time points malondialdehyde was determined in the tissue by means of TBA-test and directly by reversed phase, high pressure, liquid chromatography (HPLC). We have found no correlation between the two compared assays. During reperfusion, there was the formation of non-lipid related, malondialdehyde-like, TBA-reactive substance which leads to overestimations of the extent of lipid peroxidation. On the contrary, by direct HPLC quantitation, there was a decrease of tissue malondialdehyde during ischaemia and during the early phases of reperfusion. Our results demonstrate that TBA-test is not a reliable index of malondialdehyde accumulation in organ system.

Animals↗

PubMed1992

Occurrence of oxidative stress during myocardial reperfusion.

Reperfusion, without doubt, is the most effective way to treat the ischaemic myocardium. Late reperfusion may however cause further damage. Myocardial production of oxygen free radicals above the neutralizing capacity of the myocytes is an important cause of this reperfusion damage. There is evidence that prolonged ischaemia reduces the naturally occurring defence mechanisms of the heart against oxygen free radicals, particularly mitochondrial manganese superoxide dismutase, and intracellular pool of reduced glutathione. Consequently, reperfusion results in a severe oxidative damage, as evidenced by tissue accumulation and release of oxidized glutathione. An oxygen free radical-mediated impairment of mechanical function also occurs during reperfusion of human heart. In fact we observed during surgical reperfusion of coronary artery disease (CAD) patients, a prolonged and sustained release of oxidized glutathione; the degree of oxidative stress was inversely correlated with recovery of mechanical and haemodynamic function. These findings represent the rationale for therapeutic interventions which increase the cellular antioxidant capacities and improve the efficacy of myocardial reperfusion.

Animals↗

PubMed1992

The protective role of heat stress in the ischaemic and reperfused rabbit myocardium.

Cells subjected to increases in temperature induce the expression of several proteins known as heat shock or stress proteins. This process enhances the cell's ability to overcome the effects of further stress. In this respect, the effects of heat stress have been reported to protect the hearts of rats following ischaemia and reperfusion. We have confirmed and extended this observation, not only using different indices of myocardial injury but also in another species, namely the rabbit. Animals were anaesthetized and the body temperature raised to 42 degrees C for a 15-min period. Controls were treated in the same way but without heating. Twenty-four hours later the rabbits were re-anaesthetized and the hearts removed for either heat stress protein analysis or perfusion with Krebs buffer using an isolated perfused heart apparatus. Hearts were subjected to 60 min of low flow (1 ml/min) ischaemia followed by 30 min of reperfusion. All hearts subjected to heat stress showed an enhanced recovery of function upon reperfusion as measured by improvements in developed pressure (27.3 +/- 3.6 vs 16.3 +/- 3.0 mmHg) and diastolic pressure (37.3 +/- 7.4 vs 54.7 +/- 3.1 mmHg). In addition, creatine kinase release, associated with reperfusion, was significantly reduced in the heat-stressed hearts (532 +/- 102 vs 1138 +/- 73 mU/min/g wet wt). Myocardial accumulation and release of oxidized glutathione, an index of oxidative stress, was significantly reduced in the heat-stressed group (0.003 +/- 0.003 vs 0.376 +/- 0.113 nmol/min/g wet wt). The improved metabolic status of the reperfused heat-stressed hearts was further demonstrated by a significant conservation in the levels of ATP (6.1 +/- 0.9 vs 2.8 +/- 0.8 mumol/g dry wt) and CP (36.9 +/- 6.4 vs 16.4 +/- 5.1 mumol/g dry wt). Finally, isolated mitochondrial function in terms of respiratory control index (RCI) was maintained in the heat-stressed hearts (9.2 +/- 0.9 vs 5.7 +/- 0.2) and overloading with calcium was reduced. These data extend the hypothesis that heat stress protects the heart following ischaemia and reperfusion in this in vitro model, in a way as yet undetermined.

Adenosine Triphosphate↗

PubMed1992

PEG-SOD and myocardial antioxidant status during ischaemia and reperfusion: dose-response studies in the isolated blood perfused rabbit heart.

We have previously shown that the polyethylene glycol conjugated superoxide dismutase (SOD), which has a plasma half-life of more than 24 h, protects the blood perfused rabbit heart against injury during ischaemia and reperfusion. However, the profile for the dose-dependency of protection was bell-shaped with loss of efficacy below 6000 and above 30,000 U/kg. In the present study, isolated rabbit hearts, perfused with blood from support rabbits, were subjected to a 2 min infusion with St Thomas' Hospital cardioplegic solution followed by 60 min of global ischaemia (37 degrees C) and 60 min of reperfusion. PEG-SOD was administered 1 h or 12-24 h before ischaemia. We assessed the effect of PEG-SOD on ischaemia- and reperfusion-induced changes in: (i) the tissue content of reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) and (ii) the activity of CuZn-SOD, Mn-SOD and glutathione peroxidase and reductase (GPD and GRD). Ischaemia and reperfusion reduced tissue GSH content by 70% and increased GSSG content by 400% (from their fresh aerobic values of 13.1.9 and 0.09 +/- 0.01 nmol/mg protein, respectively). PEG-SOD, given intravenously at various doses to donor and support rabbits 1 h or 12-24 h before ischaemia, protected against these changes with a bell-shaped dose-response relationship. Thus, with 0, 3000, 6000, 12,000, 30,000 and 60,000 U/kg, GSH content was 4.1 +/- 0.4, 4.8 +/- 0.4, 8.5 +/- 0.5, 12.3 +/- 1.6, 12.3 +/- 1.6 and 5.0 +/- 0.5 nmol/mg protein in the 1 h pretreatment group and 4.1 +/- 0.4, 4.2 +/- 0.5, 10.4 +/- 1.5, 11.2 +/- 1.1, 11.4 +/- 0.7 and 4.7 +/- 0.6 nmol/mg protein in the 12-24 h pretreatment group (means +/- S.E.M.). For GSSG the corresponding values were 0.36 +/- 0.04, 0.34 +/- 0.03, 0.12 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.41 +/- 0.03 nmol/mg protein for the 1 h group and 0.36 +/- 0.04, 0.35 +/- 0.02, 0.15 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.34 +/- 0.02 nmol/mg protein for the 12-24 h group. Ischaemia and reperfusion had no effect on tissue MDA content or CuZn-SOD, GDP and GRD activity, and in general, PEG-SOD also lacked significant effect on any of these variables at any dose studied. However, Mn-SOD activity was severely reduced by ischaemia and reperfusion (from 42 +/- 7 U/mg protein in fresh aerobic controls to 6 +/- 1 U/mg protein at the end of reperfusion).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Prolonged propionyl-L-carnitine pre-treatment of rabbit: biochemical, hemodynamic and electrophysiological effects on myocardium.

Recently it has been reported that prolonged treatment with propionyl-L-carnitine, a carnitine derivative, results in a positive inotropic effect. To gain further insight into its mode of action, we pre-treated 253 rabbits for up to 10 days with daily doses of 1 mmol/kg propionyl-L-carnitine or L-carnitine intraperitoneally, using saline-treated animals as control. Twenty-four hours after the last injection, we isolated papillary muscles for electrophysiological investigations. Whole hearts were used in perfusion experiments for biochemical and hemodynamic measurements. In addition, mitochondria were harvested from these hearts for the analysis of their function. Plasma and cardiac levels of free carnitine, along with plasma short-chain acylcarnitines, increased at least two-fold after treatment with carnitine or its propionyl-ester, with concomitant rises in tissue long-chain acylcarnitine and long-chain acyl-CoA. At the time of animal sacrifice, treatment did not increase plasma or tissue propionyl-L-carnitine content. The studies carried out with perfused hearts and isolated mitochondria failed to show an effect of propionyl-L-carnitine pre-treatment on high-energy phosphate metabolism or respiration. Papillary muscles from animals, treated for 10 days, showed a lengthening of the action potential duration from 63 +/- 4 to 102 +/- 6 ms (P less than 0.001) at -10 mV. Perfused hearts from these rabbits displayed positive inotropy, as indicated by an improved pressure development at higher ventricular filling volumes, e.g., from 39 +/- 4 to 60 +/- 3 mmHg (P less than 0.05) at 3.6 ml. Pre-treatment with L-carnitine or saline failed to affect the electrophysiological and hemodynamic variables. Thus, prolonged treatment of rabbits with propionyl-L-carnitine, but not with L-carnitine, improved contractility and lengthened action potential duration in isolated muscle preparations.

Action Potentials↗

PubMed1992

Kainic acid differently affects retinal projections to different pretectal nuclei.

Kainic acid (KA) damages retinal cells, thus impairing axonal anterograde transport of labeled aminoacids when injected intravitreally. In this study, Long-Evans rats were injected with KA into one eye, and seven days later were binocularly injected with 14C-valine. The extent of residual retinal afferents to two pretectal nuclei was calculated as the percentage of the contralateral, intact side. Projections to the nucleus of the optic tract (first relay station of the optokinetic pathway) appear significantly more affected than those to the olivary pretectal nucleus (involved in the pupillary light response). These results suggest a correlation between the functional properties of retinal ganglion cells and distinctive biochemical characteristics, such as their susceptibility to KA.

Animals↗

PubMed1992

Glutamate and GABA levels in CSF from patients affected by dementia and olivo-ponto-cerebellar atrophy.

The modifications in the CSF content of glutamate and GABA in patients afflicted with primary degenerative dementia (PDD) and olivo-ponto-cerebellar atrophy (OPCA) have been evaluated. Control subjects (with disk herniation) were also included in the study. The amino-acids assays were carried out utilizing enzymatic-bioluminescence technique. GABA levels in controls were 803 +/- 98 (n = 7) and in demented patients 702 +/- 98 (n = 7) pmol/ml. Glutamate levels were 2067 +/- 244 (n = 10) in controls, 1190 +/- 81 (n = 16) pmol/ml (vs controls p less than 0.01) in demented patients, and 1116 +/- 146 (vs controls p less than 0.01) in OPCA patients. These results suggest that CSF glutamate levels in severely demented patients might be a result of generalized neuronal loss in the brain with a reactive gliosis.

Age Factors↗

PubMed1992

Isoproterenol induces release of atrial natriuretic peptide from rat atrium in vitro.

To investigate the mechanism underlying the release of atrial natriuretic peptide (ANP) in in vitro condition, isolated, superfused rat atria were subjected to adrenergic, chronotropic, and mechanical stimulation. First administration of isoproterenol (Iso; either 10(-9) or 10(-6) M) caused a release of ANP, which was transient. Subsequent increments in concentration of Iso always resulted in a much lower release of ANP, despite the increased effects on the mechanical function of the atria. Stretching of the atria resulted in a transient release of ANP. Subsequent increments in stretching were followed by decreasing release of ANP. The total score of ANP in atrial tissue after Iso and stretching was not measurably depleted. Pacing the atria with increasing frequency did not induce release of ANP. Depolarization with 40 mM KCl abolished the release of ANP in response to Iso but not the release induced by stretch. In the presence of low external Ca2+, which abolished mechanical activity, both Iso and stretch could still induce release of ANP. Propranolol abolished the release of ANP by Iso but not that induced by stretching. Prazosin did not affect the release by either stretch or Iso. Stretching the atria 20 min after administration of Iso did not cause any further release of ANP. On the other hand, adding Iso 20 min after stretching induced a release of ANP. It is concluded that Iso and stretch cause a transient release from isolated strips of atria. The amount of ANP released is not related to the dose of Iso or to the load applied. Mechanisms involved in the release mediated by the two stimuli are different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

PEG-SOD improves postischemic functional recovery and antioxidant status in blood-perfused rabbit hearts.

The isolated blood-perfused rabbit heart, subjected to 60 min of cardioplegic arrest and 60 min of reperfusion, was used to assess the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) on postischemic recovery of left ventricular developed pressure (LVDP), the tissue activity of SOD, and tissue redox state. The five groups studied were the following: PEG-SOD-free control (group A), PEG-SOD as a pretreatment and as an additive during cardioplegia and reperfusion (group B), PEG-SOD as a pretreatment and a cardioplegic additive (group C), PEG-SOD in cardioplegia alone (group D), and PEG-SOD in reperfusion alone (group E). The results show that pretreatment with PEG-SOD improves postischemic recovery of LVDP (72 +/- 2% and 66 +/- 7 vs. 47 +/- 4% in groups B, C, and A, respectively). This protection was associated with an improved tissue redox state. Thus the ischemia-induced rise in oxidized glutathione was reduced from 313 +/- 26% (group A) to 162 +/- 15 and 138 +/- 14% (groups B and C, respectively), and the fall in reduced glutathione was attenuated from 51 +/- 5% to 35 +/- 6 and 13 +/- 5%, respectively. Tissue Mn-SOD activity was also conserved from 36 +/- 4% (group A) to 71 +/- 6 and 94 +/- 4% (groups B and C, respectively). No significant effect was seen when PEG-SOD was applied in cardioplegia or during reperfusion alone.

Animals↗

PubMed1992

Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery.

BACKGROUND: The pathogenesis of salt and water accumulation in patients with chronic obstructive pulmonary disease is unclear and may differ from that in patients with congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms involved. METHODS AND RESULTS: Hemodynamics, water and electrolyte spaces, renal function, and plasma hormone concentrations were measured in nine patients with edema due to chronic obstructive pulmonary disease and in six patients after recovery. Mean cardiac output (3.8 +/- 0.26 l/min.m2) was normal, but right atrial (11 +/- 1 mm Hg) and mean pulmonary arterial (41 +/- 3 mm Hg) pressures were increased. Mean pulmonary arterial wedge pressure (11 +/- 1 mm Hg) was normal. Pulmonary vascular resistance (8.6 +/- 1.3 mm Hg.min.m2/l) was increased, but systemic vascular resistance (19.3 +/- 1.3 mm Hg.min.m2/l) and mean arterial pressure (83 +/- 4 mm Hg) were low. All patients were hypoxemic (PaO2, 40 +/- 2 mm Hg) and hypercapnic (PaCO2, 60 +/- 2 mm Hg). There was a significant increase in total body water (+21%), extracellular volume (+45%), plasma volume (+45%), blood volume (+88%), and exchangeable sodium (+38.2%). Renal plasma flow was severely reduced (-63.2%), but glomerular filtration rate was only mildly decreased (-32%). Significant increases were seen in plasma norepinephrine (3.5-fold normal), renin activity (7.6-fold normal), vasopressin (twice normal), atrial natriuretic peptide (9.4-fold normal), growth hormone (10.7-fold normal), and cortisol (1.9-fold normal). After recovery, the PaO2 increased (50 +/- 3 mm Hg) and PaCO2 fell (45 +/- 4 mm Hg), and the patients became free from edema. All the body compartments returned toward normal, although they did not entirely reach normal values. Renal plasma flow increased significantly, and glomerular filtration became normal. Right atrial and pulmonary arterial pressures and pulmonary vascular resistance decreased (p less than 0.01). Cardiac output decreased but not significantly. Blood pressure increased but not significantly. However, systemic vascular resistance increased significantly to a normal value. CONCLUSIONS: We conclude that patients with edema due to chronic obstructive pulmonary disease have severe retention of salt and water, reduction in renal blood flow and glomerular filtration, and neurohormonal activation similar to that seen in patients with edema due to myocardial disease. However, unlike the latter, in chronic obstructive pulmonary disease cardiac output is normal, and systemic vascular resistance and arterial blood pressure are low. This probably is due to the vasodilator properties of hypercapnia. The consequent low arterial blood pressure may be the stimulus for the neurohormonal activation and retention of salt and water.

Adult↗

PubMed1992

Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action.

We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state. At concentrations > 10(-6) M, zofenopril, but not captopril, caused a reduction in myocardial NE content. At 10(-4) M, both drugs caused a reduction in developed pressure and an increase in diastolic pressure and release of creatine phosphokinase (CPK). Second we investigated their effects on ischemic and reperfused myocardium. Both drugs exerted a cardioprotection; zofenopril was always more potent than captopril. Recovery of developed pressure on reperfusion improved, and peak release of NE was reduced, as was release of CPK. Calcium homeostasis and mitochondrial function were maintained. Captopril had no effect on occurrence of oxidative stress during reperfusion, whereas zofenopril reduced it. In hearts treated with the converting enzyme inhibitors, peak release of NE was correlated to mitochondrial calcium content, production of ATP, and recovery of mechanical function on reperfusion. These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE.

Adenosine Triphosphate↗

PubMed1992

Stunned and hibernating myocardium: possibility of intervention.

There are several potential outcomes of myocardial ischemia. When ischemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. When myocardial ischemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function. Under these conditions, reperfusion restores complete contractile performance. This type of ischemia, leading to a reversible, chronic left ventricular dysfunction, has been termed hibernating myocardium. The difference between this condition and that described before, i.e., prolonged ischemia, which results in further damage on reperfusion, is, most likely, related to residual coronary flow. In the hibernating myocardium, which is always supplied by a narrow coronary artery, blood flow is not low enough to cause progression toward tissue necrosis, but it is low enough to cause pH changes that, in turn, are responsible for the downregulation of myocardial contractility. The level of underperfusion is sufficient to maintain aerobic metabolism of the quiescient myocardium as demonstrated by the absence of lactate and creatine phosphokinase release. There are no doubts that revascularization is essential for hibernated myocardium, and the clinical goal to achieve is the possibility of accurately distinguishing viable from infarcted tissue. A third possible outcome of myocardial ischemia is a postischemic ventricular dysfunction or myocardial stunning. This term describes a transient mechanical dysfunction that persists on reperfusion after a short period of ischemia, despite the absence of irreversible damage. There are numerous clinical conditions in which stunning might manifest.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗