Reperfusion of isolated rabbit heart after 60 min of ischaemia resulted in poor recovery of mechanical function, release of reduced (GSH) and oxidized glutathione (GSSG), reduction of tissue GSH/GSSG ratio and shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. Pretreatment of the isolated heart with propionyl-L-carnitine (10(-7) M) improved the functional recovery of the myocardium, reduced GSH and GSSG release and attenuated the accumulation of tissue GSSG. This effect was specific for propionyl-L-carnitine as L-carnitine and propionic acid did not modify myocardial damage.

Animals↗

PubMedDate not supplied

Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion.

In the heart mitochondria exert two roles essential for cell survival: ATP synthesis and maintainance of Ca2+ homeostasis. These two processes are driven by the same energy source: the H+ electrochemical gradient (delta microH) which is generated by electron transport along the inner mitochondrial membrane. Under aerobic physiological condition mitochondria do not contribute to the beat to beat regulation of cytosolic Ca2+, although Ca2+ transient in mitochondrial matrix has been described. Increases in mitochondrial Ca2+ of mumolars concentration stimulate the Krebs cycle and NADH redox potential and, therefore, ATP synthesis. Under pathological conditions, however, mitochondrial Ca2+ transport and overload might cause a series of vicious cycles leading to irreversible cell damage. Mitochondrial Ca2+ accumulation causes profound alterations in permeability of the inner membrane to solutes, leading to severe mitochondrial swelling. In addition Ca2+ transport takes precedence over ATP synthesis and inhibits utilization of delta microH for energy production. These processes are important to understand the sequence of the molecular events occurring during myocardial reperfusion after prolonged ischaemia which lead to irreversible cell damage. During ischaemia an alteration of intracellular Ca2+ homeostasis occurs and mitochondria are able to buffer cytosolic Ca2+, suggesting that they retain the Ca2+ transporting capacity. Accordingly, once isolated, even after prolonged ischaemia, the majority of the mitochondria is able to use oxygen for ATP phosphorylation. When isolated after reperfusion, mitochondria are structurally altered, contain large quantities of Ca2+, produce excess of oxygen free radicals, their membrane pores are stimulated and the oxidative phosphorylation capacity is irreversibly disrupted. Most likely, reperfusion provides oxygen to reactivate mitochondrial respiration but also causes large influx of Ca2+ in the cytosol as result of sarcolemmal damage. Mitochondrial Ca2+ transport is therefore stimulated at maximal rates and, as consequence, the equilibrium between ATP synthesis and Ca2+ influx is shifted towards Ca2+ influx with loss of the ability of ATP synthesis.

Adenosine Triphosphate↗

PubMedDate not supplied

Particular outcomes of myocardial ischaemia: stunning and hibernation.

There are several potential outcomes of myocardial ischaemia. When ischaemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. When myocardial ischaemia 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 ischaemia, 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 ischaemia, which results in further damage on reperfusion, is, most likely, related to residual coronary flow. In the hibernating myocardium, which is 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 intracellular changes and adaptative mechanisms which, in turn, are responsible for the down-regulation of myocardial contractility and for the preservation of viability. The level of underperfusion is sufficient to maintain aerobic metabolism of the quiescent myocardium as demonstrated by the absence of lactate and creatine phosphokinase releases. There are no doubts that revascularization is essential for hibernating myocardium, and the clinical goal to achieve is the possibility of accurately distinguishing viable from infarcted tissue. A third possible outcome of myocardial ischaemia is a post-ischaemic ventricular dysfunction or myocardial stunning. This term describes a transient mechanical dysfunction that persists on reperfusion after a short period of ischaemia, despite the absence of irreversible damage.

Animals↗

PubMedDate not supplied

Cardiovascular effects induced by the injection of a new nonionic contrast medium (Iopamidol): experimental study in dogs.

The hemodynamic effects induced by the injection in the pulmonary artery of the new nonionic water soluble contrast medium Iopamidol were compared with those obtained by the injection of two other currently used contrast media (meglumine diatrizoate and sodium iothalamate). The experiments were carried out in nine mongrel dogs. Hemodynamic variables were continuously measured prior to, during, and for 8 minutes after injection of the contrast media. Injections of iopamidol produced significantly smaller decreases in aortic pressure (p less than 0.01), contractile indices (p less than 0.01), and peripheral resistances (p less than 0.01), and changes in heart rate and in cardiac output were less pronounced. At 3-4 minutes after injection, an increase in Vmaxd was observed with all three contrast media, but it was significantly lower after injecting Iopamidol. The role of hyperosmolality in causing cardiovascular changes is discussed. The less significant changes induced by Iopamidol appear to be the result of its lower osmolality, which is about a third that of meglumine diatrizoate or sodium iothalamate.

Animals↗

PubMedDate not supplied

Noninvasive evaluation of the effects of oral ibopamine (SB 7505) on cardiac and renal function in patients with congestive heart failure.

We investigated the effect of oral ibopamine (SB 7505) on myocardial and renal function in eight patients suffering from congestive heart failure. Ibopamine was administered orally 50 mg twice a day for 7 days. Systolic time intervals PEP (preejection period) and EMS (electromechanical systole) decreased significantly after each administration of ibopamine. Maximum reduction of systolic time intervals was observed 4 h after ibopamine administration. Statistically significant shortening was still apparent at 8 h. Twenty-four hour urinary volume was greater than control values on each day of ibopamine administration. The average daily increase in urine output was 70.2%. Sodium and potassium excretion increased. Each patient showed symptomatic improvement during therapy. No side effects attributed to ibopamine therapy were observed, and clinical laboratory values were unchanged. Tachyphylaxis was not observed during the period of treatment. We conclude that oral administration of ibopamine improves cardiovascular performance and renal function in patients with congestive heart failure.

Aged↗

PubMedDate not supplied

Hemodynamic effects of ibopamine in patients with idiopathic congestive cardiomyopathy.

We administered 150 mg of ibopamine orally to 10 patients suffering from idiopathic congestive cardiomyopathy. Hemodynamic function was evaluated by right heart catheterization and by measurement of cardiac output with the thermodilution technique. Ibopamine caused no significant change in heart rate or mean arterial pressure. Cardiac index, stroke volume index, and left ventricular work index all increased significantly by about 30%. Mean pulmonary arterial pressure decreased by about 30%, and systemic vascular resistance decreased by about 20%. The effects peaked at about 3 h and lasted 5-7 h. No side effects were noted. These findings with invasive techniques confirm those of others using noninvasive techniques, and suggest that ibopamine may be useful in the treatment of congestive heart failure.

Adult↗