Reperfusion injury in ischemic myocardium: effects of nifedipine and verapamil.

Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Calcium entry into myocytes has been implicated in this effect, and calcium channel-blocking agents have been used in attempts to prevent or limit such damage. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either nifedipine or verapamil (both clinically employed calcium channel-blocking agents) prior to and during coronary reperfusion. During reperfusion, nifedipine produced a lowering of mean arterial pressure, while mean arterial pressure was constant in verapamil-treated pigs and rose in pigs not receiving drugs. Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were independently graded on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for nifedipine-treated animals than for controls. Ischemic damage in verapamil-treated pigs was not different from that seen in control animals, except for a slight improvement in myofibrillar appearance. We conclude that nifedipine, administered prior to and during reperfusion of myocardium, protects against reperfusion injury. The mechanism of this protective effect may be attributable, in part, to afterload reduction and, in part, to inhibition of transmembrane calcium flux in cardiac fibers.

Reperfusion injury in ischemic myocardium: protective effect of controlled reperfusion.

Restoration of coronary artery flow following a period of ischemia often results in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have compared the ultrastructural effects of uncontrolled reperfusion in vivo of ischemic pig myocardium with the ultrastructural effects of reperfusion controlled at flow rates comparable to preischemia levels. Myocardial ischemia was produced for 60 minutes in 9 pigs by means of a reversible coronary artery occlusion, after which coronary artery flow was restored for 120 minutes. This restoration of flow was complete in four pigs (resulting in uncontrolled reperfusion) and partial in five pigs, with constant monitoring and adjustment of flow to maintain rates near preischemia values (controlled reperfusion). Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and ischemic depletion of glycogen were graded independently and blindly by two investigators using a simple, nonparametric three-point scale. Ischemic damage was greater in pigs receiving uncontrolled reperfusion than in animals receiving controlled reperfusion, and these differences were significant for ischemic effects on nuclei (p less than 0.01), glycogen (p less than 0.02), and myofibrils (p less than 0.05) but not for ischemic effects on mitochondria (p = 0.095). We conclude that uncontrolled, hyperemic flow during reperfusion of ischemic myocardium is responsible, in part, for the phenomenon of reperfusion injury.

Quantitation of postexercise lung thallium-201 uptake during single photon emission computed tomography.

To test the hypothesis that analysis of lung thallium uptake measured during single photon emission computed tomography (SPECT) yields supplementary clinical information as reported for planar imaging, quantitative analysis of lung thallium uptake following maximal exercise was performed in 40 clinically normal subjects (Group 1) and 15 angiographically normal subjects (Group 2). Lung thallium uptake was measured from anterior projection images using a ratio of heart-to-lung activities. Seventy subjects with coronary artery disease (CAD) (Group 3) determined by angiography (greater than or equal to 70% luminal stenosis) underwent thallium perfusion SPECT. Thirty-nine percent of these subjects had multivessel and 61% had single vessel CAD. Lung thallium uptake was elevated in 47 of 70 (67%) Group 3 subjects. Group 3 subjects with elevated lung thallium uptake did not differ from Group 3 subjects with normal lung thallium uptake with respect to extent or distribution of coronary artery disease, left ventricular function, or severity of myocardial ischemia as determined by exercise and redistribution thallium SPECT. Thus, the measurement of thallium lung uptake from anterior projection images obtained during SPECT frequently identifies patients with CAD, but it may not provide supplementary information regarding the extent of myocardial ischemia or ventricular dysfunction.

Reperfusion injury in ischemic myocardium: protective effects of ruthenium red and of nitroprusside.

Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Ruthenium red is an inorganic dye with calcium flux-inhibiting properties which protects ischemic myocardium against reperfusion damage, as judged by biochemical indices of mitochondrial function. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either ruthenium red or nitroprusside (an after-load reducing agent with no known calcium flux-inhibiting properties) prior to and during coronary reperfusion. During reperfusion, both ruthenium red and nitroprusside produced similar lowering of mean arterial pressure, while mean arterial pressure rose in pigs not receiving these drugs. Myocardial samples from the ischemic reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were graded independently on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for treated animals than for controls. This protective effect was similar for both ruthenium red-treated animals and nitroprusside-treated animals. These results suggest that the protective effects of ruthenium red treatment are attributable to its afterload reducing properties rather than to inhibition of transmembrane calcium flux in cardiac fibers.