As worded, the question "Should silent ischemia be treated?" needs to be examined carefully, assuming that silent ischemia is even the correct topic of the question. The way the question is phrased influences the answer. The more the question's permutations are examined, the clearer it becomes that the problem is one of definition. Our conceptualization of the ischemic process is still incomplete, and the question of whether to treat silent ischemia remains. Ultimately, the decision will depend on demonstrable benefit for prognosis. Every acute ischemic syndrome is indicative of poor prognosis, independent of other factors associated with adverse outcome and of the method of measurement. The true determinant of the need to treat is the total ischemic pattern, and how silent ischemia and angina fit within that context is not yet known.

alpha-1 acid glycoproteins become elevated in the patient's serum within a few hours after an acute myocardial infarction. Previous reports have suggested a correlation between the magnitude of this elevation and infarct size as estimated by enzyme markers. Correlation has also been observed between the mortality following infarction and appearance of elevated alpha-1 acid glycoproteins. We now report that these glycoproteins are detectable in normal myocardium using immunohistochemical techniques. Diminished amounts are observed in necrotic tissue in acute myocardial infarcts. Ultrastructural localization by immunoelectron microscopy using sections of normal myocardium established the presence of alpha-1 acid glycoproteins primarily at the cell surface in the region of the sarcolemma. The observations suggest that myocardium may directly contribute to the elevation of serum alpha-1 acid glycoproteins after an infarct, and the assessment of these components may serve as an additional serum marker.

Studies of the mechanisms and characteristics of ischemic heart disease have increasingly documented evidence of myocardial ischemia in the absence of symptoms. Recent work using objective criteria of ischemic events has confirmed that angina pectoris or its equivalents need not accompany true myocardial ischemia, and this appears to be quite common. The impact of these findings on prognosis awaits further study, but preliminary data suggest an improved prognosis for persons in whom coronary artery disease remains asymptomatic compared with symptomatic patients. Further, reduction of silent ischemic events with nitrate therapy may be associated with a more benign subsequent course. Preliminary trials show a reduction of the number, duration and magnitude of silent ischemic events by transdermal nitroglycerin. Ongoing technical innovations in monitoring systems should allow more complete characterization of this syndrome and lead to definition of medical therapy for it.

Using agarose gel electrophoresis MB-creatine kinase (MB-CK) activity was examined in the serum of 120 patients with acute alcohol intoxication admitted to a detoxification ward. Total CK activity was increased in 67 percent of patients and MB-CK activity was increased in 8.3 percent. Alcoholic patients also were studied by Sephadex chromatography and, in seven cases, MB-CK was greater than three standard deviations from the normal. Thus, this study demonstrates that acute alcohol intoxication is associated with increased MB-CK activity. These findings raise the possibility that excessive alcohol ingestion may lead to acute myocardial injury.

Intermittent vasospasm and/or platelet aggregation may play an important role in producing transient coronary artery obstruction leading to an unstable ischemic syndrome. To determine whether intravenous infusion of prostaglandin E1 (PGE1) a known coronary vasodilator and inhibitor of platelet aggregation, produces salutary effects in unstable angina, we evaluated its effects in 19 patients with an unstable acute ischemic syndrome. PGE1 produced a significant decrease in the number of episodes of rest angina (p less than 0.001) and eliminated the need for intravenous nitroglycerin and morphine in 10 patients. These salutary clinical effects were associated with a significant (p less than 0.05) reduction in mean arterial pressure, mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, and the double product, without a reduction in the endocardial perfusion gradient (aortic diastolic blood pressure--mean pulmonary capillary wedge pressure). Adverse effects were generally minor and easily controlled. Thus PGE1 infusion may be of value in the treatment of acute unstable ischemic syndromes.

We utilized immunoperoxidase methods to study the distribution of CK-B and CK-M in normal, ischemic and necrotic myocardium. Human myocardium was obtained from autopsy (n = 10) and surgery (n = 16). Cardiac tissue from 22 dogs with experimental myocardial infarction induced by closed-chest coronary balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery blood flow for 3 h were studied. Duration of occlusion was 45 min (n = 2), 3 h (n = 8), 5 to 6 h (n = 7), 15 to 24 h (n = 5). Highly purified anti-CK-B and M were prepared in our laboratory and obtained commercially. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for CK-B and CK-M. Necrotic myocardium from patients with acute infarcts (10 to 24 h old) showed markedly reduced immunostaining. In dogs with 3 to 24 h occlusion immunostaining was significantly reduced for both CK-B and CK-M in regions confirmed to be necrotic by triphenyl tetrazolium chloride (TTC) and H & E staining. Myocardial necrosis was confirmed in the 3-h infarcts by electron microscopy (EM). In the four dogs with a 50% reduction in left main flow for 3 h, ischemia was demonstrated by glycogen loss in periodic acid-Schiff stained-sections; but there was no evidence of necrosis by EM or TTC, and there was no loss of immunostaining evident for CK-B and CK-M. Thus, using immunoperoxidase techniques, CK-B and CK-M were visualized in normal and ischemic myocardium, with decreased staining in necrotic tissue. These findings indicate that cell death is necessary for the demonstration of CK-M and CK-B loss from the myocardium by this technique.

Recent studies suggest that the QRS scoring system (QRSs) using observations of Q- and R-wave duration and RQ and RS amplitude ratios in the standard electrocardiogram (ECG) is useful in estimating left ventricular function after acute myocardial infarction (AMI).

Large doses of morphine sulfate have been reported to cause myocardial lactate production and reduction in coronary blood flow in animals. Similar effects with clinical doses in man would significantly alter the management of cardiac patients. Eleven adult patients with significant coronary arterial disease and normal left ventricular ejection fraction were studied before and 30 minutes after infusion of morphine (0.25 mg/kg IV). Evaluation of myocardial metabolism showed an increase in coronary sinus oxygen content (p less than 0.001) and a reduction in myocardial oxygen consumption. Myocardial lactate extraction was not altered. No change in coronary sinus blood flow was seen. It is concluded that infusion of morphine sulfate, 0.25 mg/kg IV, does not produce global myocardial ischemia in patients with coronary artery disease and normal ventricular function.

Myocardial beta-adrenoceptor binding was investigated, with (-)3H dihydroalprenolol as radioligand, in microsomes derived from anterior (ALV) and inferior (ILV) myocardial wall sections of the canine left ventricle. Characterisation of specific binding sites revealed a hierarchy of myocardial beta-adrenoceptor binding with greater binding occurring to the anterior than the inferior wall of the left ventricle, under identical experimental conditions. Equilibrium analysis by Scatchard plots suggested a significant (P less than 0.01) difference in the number of receptors (Bmax ALV = 70 fmol . mg-1 protein vs Bmax ILV = 37 fmol . mg-1 protein) with no alteration in the binding affinity of the receptors (KDALV = 10.1 nmol . litre-1 vs KDILV = 6.7 nmol . litre-1). Such differences in the extent of binding of beta-adrenoreceptors in cardiac muscle may be of physiological and pathological significance and may account for the heterogeneity of regional autonomic responses in the heart.

The early release patterns of MB-creatine kinase (CK-MB) in myocardial ischemia and infarction are largely unknown. We utilized a sensitive column Chromatographic assay of CK-MB activity (precision = 1.1 IU/liter) and sequential CK-MB samples were obtained during the first 6 hours of illness to define the early time course of enzyme release. The average CK-MB in 39 normal subjects was 2.4 ± 0.93 (mean ± standard deviation (SD)). Twenty-two patients with ischemic chest pain, in whom myocardial infarction did not develop, were characterized by normal CK-MB's (2.4 ± 1.0). Of 39 patients in whom transmural myocardial infarction developed, 28 (72 percent) were found to have abnormal CK-MB either initially or over a 20-minute sampling period. In contrast, 100 percent of the patients considered to have sustained a nontransmural myocardial infarction had abnormal initial CK-MBs and subsequently demonstrated significant increases in CK-MB from 28 ± 19 initially to 41 ± 30 lU/liter (P < 0.01, N = 16) over the 20-minute sampling period. Thus, CK-MB appears earlier in plasma following nontransmural myocardial infarction than transmural myocardial infarction, probably reflecting perfusion to ischemic myocardium.