We hypothesized that oxidative processes in myocardial tissues initiated by ischemia also cause the same kind of changes in blood proteins and lead to oxidation of sulfhydryl groups (SH). To test this hypothesis, the ratio (%MA) of mercaptalbumin to total albumin (=mercaptalbumin+nonmercaptalbumin) and the total SH contents of serum were measured in patients with coronary artery disease. There was a positive correlation between %MA and total SH contents and both values were reduced in propotion to the severity of the coronary artery disease. Furthermore. these values were lower early hours after the onset of acute myocardial infraction than 4 weeks later. These results sup-port our hypothesis, and may provide a basis for the administration of agents which can counteract oxidative stress in order to protect myocardium in patients with coronary artery disease.

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Twenty-four hour ECG recordings of 132 patients with frequent (>1000/day) ventricular premature contractions (VPCs) were analyzed using a computerized system, designed to evaluate the relationships between 1) the VPC frequency and heart rate (HR) (VPC-HR relation), 2) the coupling interval (CI) of VPCs and HR (CI-HR relation), and 3) the incidence of ventricular tachycardia (VT) and HR (VT-HR relation). The patterns of the VPC-HR relation included: 1) an increase in VPCs with increasing HR (positive correlation, 43 patients), 2) an increase in VPCs at low HR range and a decrease at high HR range, with increasing HR (bidirectional correlation. 74 patients), 3) a decrease in VPCs with increasing HR (nagative correlation, 7 patients) and 4) constant VPCs over all HRs (flat correlation. 8 patients). Patients were divided into 2 broad categories according to whether they had a positive correlation (P group, 43 patients) or the other correlations (non-positive or NP group, 89 patients). Of 132 patients, the CI-HR relation was negative in 129 (98%) and positive in only 3 (2%). Patients with frequent VTs (10 or more events over 24h) were significantly more frequent in the P (9 patients. 21%) than in the NP group (7 patients, 8%, p<0.05). However, mean HR, mean CI, total VPC counts and the slope of CI-HR relation were not significantly different between the groups. The VT-HR relation observed in 16 patients with frequent VTs were positive in 9 of the P group and In 2 of the NP group and non-positive in 5 of the NP group. We conclude that: 1) the incidence of VTs depends on underlying HR, as was the case for VPCs, 2) in most (88%) patients, the occurrence of VPC and VT reveals similar dependence on the underlying HR, and 3) the CI of VPCs shortens as HR increases in most (98%) patients.

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Seventy-one consecutive patients undergoing cardiac surgery for acquired valvular diseases were analyzed to determine the incidence of and the predisposing factors to postoperative ventricular arrhythmias. We recorded the Holter ECGS before (pre-op), and within 24h (op-day) and 4 to 10 weeks after operation (post-op) and determined the frequency of ventricular arrhythmias and the degree according to the Lown grade. The relationship between the op-day ventricular arrhythmias and clinical, hemodynamic, operative or postoperative variables was examined. The operation included mitral valve replacement or open mitral commissurotomy (49 patients, group M), aortic valve replacement (12 patients, group A) and a combined mitral and aortic operation (10 patients. group A+M). In all groups, the frequency and the degree of ventricular arrhythmias increased at the op-day and decreased at the post-op period approximately to the pre-op level. The frequency and Lown grade of the 3 groups were similar in each of the pre-op, the op-day and the post-op periods. The frequency and Lown grade of the op-day ventricular arrhythmias increased with increases in the arrhythmia frequency and Lown grade at the pre-op period, and in patients with left ventricular (LV) dysfunction at the post-op period, as evidence by an increased LV volume and decreased ejection fraction on echocardiograms. Furthermore, the frequency of ventricular premature contractions in the op-day was significantly less when a cardioplegia solution containing magnesium was used than in the case of a cardioplegia solution without magnesium. The op-day ventricular arrhythmias showed no significant relation to extracorporeal ciuculation time, aortic cross-clamping time, the antiarrhythmic drugs used and the op-day serum levels of K and CK-MB.

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We describe a 61-year-old woman with tetralogy of Fallot and dextrocardia with complete situs inversus. The functional status of this patient was New York Heart Association (NYHA) class II and the systemic blood pressure was 100/54mmHg. The hematocrit was 54.4% and the arterial partial pressure of oxygen was 53mmHg. On cardiac catheterization, both pulmonary valvular and infundibular stenoses were of equal severity and the aorta and main pulmonary artery were of equal size. We think that this patient has survived to this unusual age for tetralogy of Fallot because of unusually low systemic pressure and a proper balance between the ventricular septal defect and the pulmonary stenosis.

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Interventricular septal involvement in myocardial infarction is usually associated with infarction of the left ventricular anterior free wall, as the obstruction is at the major portion of the left anterior descending coronary artery. Acute myocardial infarction with obstruction only of the first septal branch is rare. We describe here a case of pure septal infarction. The case was diagnosed by emergency coronary arteriogram (CAG). Although the patient had a large first septal branch, his global left ventricular function was preserved. Abnormal findings were localized in only septal region as determined by left ventriculography (LVG), two-dimensional echocardiography (2DE), and ^99mtechnetium pyrophosphate (^99m Tc-PYP) and ²⁰¹thallium (²⁰¹Tl) myocardial scintigraphy.

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The effects of denopamine (a beta₁-selective adrenergic receptor agonist) and isoproterenol (a non-selective beta-adrenergic receptor agonist) on heart rate. left ventricular contractility, and left ventricular oxygen consumption (VO₂) at the same left ventricular volume were compared in excised cross-circulated dog hearts. Denopamine and isoproterenol increased heart rate and VO₂ to a comparable extent at a comparably increased contractility. Moreover, the oxygen cost of contractility which quantifies VO₂ for excitation-contraction coupling was the same between the two agents. These findings contradict the previously reported smaller increases in heart rate and VO₂ by denopamine than by isoproterenol in open-chest dog hearts, which have been mainly attributed to the beta₁-selectivity of denopamine. Our results suggest that in isolated and denervated hearts. the degree of beta₁-selectivity of a beta-agonistic agent does not directly determine the relative potencies of its inotropic and chronotropic effects and the oxygen cost of contractility.

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We studied the importance of reflow after reperfusion for myocardial salvage. In 19 open-chest dogs, the left anterior descending coronary artery was occluded for 3h and then reperfused. Non-radioactive colored microspheres were injected into the left atrium to measure regional myocardial blood flow (RMBF). Immediately after occlusion. RMBF was reduced to 23±2% (of control) in the inner layer and 32±2% in the outer layer. Five minutes after reperfusion. RMBF was increased to 170±20% and 156±11% of control in the inner and outer layers, respectively. One week later. RMBF in the inner layer was reduced to 63±4% but it was not reduced (100±6%) in the outer layer. There was a roughly positive correlation between the inner/outer flow ratio measured 5 min after reperfusion and myocardial creatine kinase activity. Myocardial necrosis determined by triphenyl tetrazolium chloride stain varied inversely with the inner/outer flow ratio. These results indicate that good reflow in the inner layer 5 min after reperfusion is a favorable indicator for myocardial salvage.

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We have performed immunocytochemical investigations on the distribution of various cell types and proliferating cells in human atherosclerotic lesions. Studies include fibrocellular tissue response following percutaneous transluminal coronary angioplasty (PTCA) or aortocoronary (A-C) bypass operation using monoclonal antibodies specific to smooth muscle cells, macrophages. endothelial cells, lymphocytes and proliferating cell nuclear antigen (PCNA). All studies were performed on methanol-Carnoy's-fixed. paraffin-embedded tissues. The cellular composition of the following three types of raised lesions were analyzed: 1) fibro-fatty lesions composed almost exclusively of macrophages: 2) fibrous lesions predominantly composed of smooth muscle cells; 3) advanced plaques characterized by complex layers of smooth muscle cells and macrophages with considerable variation from region to region. Also noted were foci of medial and even intimal vascularization subjacent to the more advanced plaques. Cells encountered within the fibrous intimal thickening in the vein graft or fibrocellular tissue reponse following PTCA were predominantly smooth muscle cells in origin. Some cells were PCNA-positive. These studies demonstrate the application of monoclonal antibody technology to the study of the cellular composition and cell kinetics of human atherosclerotic lesions.

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To elucidate the mechanism of migration of vascular smooth-muscle cells (SMCs) from media to intima, we have investigated the phenotypic modulation of the medial SMC at bifurcation of the celiac artery in 5 children and 3 young persons using a transmission electron microscope. We counted the number of separated SMCs from the elastic layers. although the medial SMCs are fundamentally attached to the elastic fibers. and are still contractile in their phenotypes. Both proximal and distal portions revealed that SMCs in the media were more or less present in the separated state and were ultrastructurally consistent with the synthetic state of SMC in the proximal area and the contractile state in distal areas. In order to migrate from media to intima. medial SMC should separate from the elastic layers and transform their phenotypes. In this paper. we examined the relationship between vascular SMCs and elastic layers in the media and ascertain that it was responsible for the contribution to the subsequent phenotypic modulation and their migration of medial SMCs.

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Atheroscrelosis is associated with an accumulation of proteoglycans. Proteoglycans and/or glycosaminoglycans, in particular heparan sulfate, produced by endothelial cells are thought to play important roles in diverse vascular functions. Of particular note is that they possess anticoagulant functions, i.e., heparin-like antithrombin cofactor activity. Incubation of antithrombin III with endothelial cell cultures resulted in a specific, saturable binding of this protease inhibitor presumably to the endothelial cell surface. In addition, thrombin inactivation by antithrombin III was accelerated on the endothelial surface, providing strong evidence that heparan sulfate on the surface of endothelial cells exerts a heparin-like activity. β-D-xyloside or cytokine treatments altered the synthesis of heparan sulfate on the endothelial cell surface, resulting in decreased antithrombin III binding and diminished heparin-like anticoagulant activity of endothelial cells. The modulation of endothelial heparin-like compounds by these pharmacologic or physiologic agents may have pathophysiologic implications in thrombosis as well as atherogenesis.

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Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa single chain polypeptide, which stimulates the growth and chemotaxis of endothelial cells in vitro and angiogenesis in vivo. Purification from human platelets and cDNA cloning of PD-ECGF disclosed that it is a novel type of angiogenic factor without sequence similarity to hitherto known proteins. PD-ECGF is present in human platelets as well as in placenta. Amino acid sequencing of PD-ECGF from human placenta revealed that the placental form has an additional 5 amino acids at the N-terminus. In cultured cells. it is produced by normal fibroblasts as well as some transformed cell lines. PD-ECGF lacks a hydrophobic signal sequence and remains inside the producer cells. PD-ECGF may act at sites of injuty as a wound hormone and thus play an important role under several physiological and pathological conditions.

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Distinct genes encode a and p PDGF receptors which differ in their abilities to be triggered by three dimeric forms of the PDGF molecules. By use of a strategy involving introduction of expression vectors for α and β PDGF receptor cDNA into the cells originally lacking these receptors, we demonstrated that each receptor was able to couple independently with mitogenic signal transduction pathways inherently present in these cells. Moreover. both receptors were capable of inducing a readily detectable chemotactic response. The vascular smooth muscle cells which express both types of PDGF receptors are mitogenic and chemotactic for PDGFs. Moreover, the a receptor is the prefer-red receptor for platelet PDGF-AB as well as the PDGF-AA isoform which is ubiquitously produced in many cells forming atherosclerotic plaques including macrophages, endothelial cells and even arterial smooth muscle cells. Our results indicated that the availability of specific PDGF isoforms and the relative expression of each receptor gene product appear to be major determinants of the PDGF response. An understanding of the mechanisms by which the expression of PDGF and their receptors on vascular smooth muscle cells are regulated will give greater insights as to how these gene products are involved in atherosclerosis.

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In bovine aortic smooth muscle, GTP-binding activity was equally distributed in the membrane and cytosol fractions. The most abundant GTP-binding proteins (G proteins) in each fraction were purified to near homogeneity and characterized. The most abundant G protein in the membrane fraction had a Mr value of about 22, 000 (m22K G) as estimated on sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE). m22K G and the human platelet smg p21, a ras p21 like G protein having the same effector domain as ras p2ls, were eluted at the same retention time on C₄ reversed-phase high performance liquid chromatography (HPLC). Moreover. m22K G was specifically recognized by an anti-smg p21 polyclonal antibody. m22K G was phosphorylated by cyclic AMP-dependent protein kinase with a stoichiometry of one phosphate/molecule of protein. The most abundant G protein in the cytosol fraction had a Mr value of about 21, 000 (c21K G) as estimated on SDS-PAGE. c21K G was ADP-ribosylated by botulinum ADP-ribosyltransferase and about 0.4 mol of ADP-ribose was maximally incorporated into 1 mol of c21K G. c21K G and the bovine brain rhoA p21, another ras p21 like G protein, were eluted at the same retention time on C₄ reversed-phase HPLC and migrated at the same position on two-dimensional gel electrophoresis. These results indicate that the major G proteins in the membrane and cytosol fractions of bovine aortic smooth muscle are smg p21 and rhoA p21, respectively. Possible roles of these G proteins in vascular smooth muscle are discussed.

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