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Notes: Summary Following acute myocardial infarction the functional load of the surviving heart muscle does increase considerably, leading to an increased release of adrenergic neurotransmitters with a consequent decrease in endogenous catecholamine stores. Within the first 24 h following infarction, a temporary decline in the high-energy phosphate content is observed in the surviving heart muscle; furthermore, a reduction in lactate extraction is noted. In the intact organism an increased shortening of the surviving heart muscle is noted as a consequence of the altered ventricular geometry and the increased release of catecholamines. If these effects are excluded by means of isolation and analysis in vitro, a decrease in contractile function could be demonstrated in the surviving heart muscle in the early phase following infarction; the response to positive inotropic interventions was depressed as well. These changes are reversible; six weeks following infarction a normal contractile behaviour is observed.

Notes: Summary The first successful heart-transplantation carried out in the Department for Cardiovascular Surgery of the University of Munich, Klinikum Großhadern is reported. The recipient, 32 years old at the time of operation, had sustained a large antero-lateral-septal myocardial infarction in June 1980; thereafter the left ventricular ejection fraction was severely impaired (e.f.=19%). Yet, the operation was definitely planned some year later, after the patient had survived an embolus to the right lung, an acute left heart failure and a small ulcer of the stomach. The operation was performed on 8-19-1981. The donor was a 23 year old young man, who had met a fatal motorcycle accident 10 days ago. The man was pronouned dead in the afternoon of the preoperative day according to the criterions of the German Society for Surgery by means of a carotid angiogram. Donor and recipient were well matched in regard to blood group, HLA-A2-System and finally crossmatch-test. Transplantation was carried out according to the technique of Lower and Shumway. Immediately p.o., immunosuppressive therapy was started using azathioprine, cortisone and antihuman thymocyte globulin. Two acute rejections were noted, the first from p.o. day 6 to 15, the second from p.o. day 22 to 34. The second acute rejection was complicated by a pneumatosis cystoides intestinii, which caused a change of the immunosuppressive therapy to Cyclosporin A. No further complications were registered in the following p.o. course, the patient is discharged since Christmas 1981.

Notes: Summary On 121 consecutive patients with coronary heart disease coronary angiography and quantitative left ventricular angiography was done with the view to aortocoronary bypass surgery. 24 (20%) had mitral regurgitation (MR) by angiographic criteria, 20 of them had MR grade I/IV, four had MR II/IV. In 23 out of 24 patients with MR quantitative left ventriculography revealed localized contraction disorders. MR was clinically diagnosed in 15 out of 24 patients. In eleven patients (48%) contraction abnormalities were localized in the inferior wall, in five cases (22%) in the anterior wall and in seven cases (30%) both in the anterior and posterior wall. Of the latter group patients with MR showed a significantly lower ejection fraction than patients without MR (p〈0,05). Furthermore the MR-group showed larger akinetic areas, preferentially located in the inferior segments 0°–240° and in the anterolateral segments 60°–90°. Three vessel disease was more frequent in this group (43%) than in the group without MR (23%). Patients with inferior wall asynergy frequently showed combined stenosis or occlusion of the right and circumflex coronary artery. In conclusion, MR in coronary heart disease is most often associated with localized contraction disorders of the left ventricle; posterior wall infarctions, multiple vessel disease and large akinetic areas are more frequent. However, the hemodynamic significance of MR in patients with chronic myocardial infarction is usually insignificant.

Notes: Summary The evaluation of ventricular compliance by means of the diastolic pressure—volume relationship encounters difficulties because of its curvilinear nature and dependency on alterations in ventricular size and geometry. The slope of the functiondp/dV:P, wheredp/dV is the first derivative of the pressure—volume curve is largely linear. The extrapolation of this finding to in vivo conditions is made possible utilizing the ratio of the diastolic pressure-volume differenceDP/DV. This relationship was determined in 20 subjects with coronary heart disease and in 6 subjects judged to be without heart disease, utilizing catheter-tip manometry and determination of diastolic volume change.DV was taken as stroke volume in the absence of intracardiac shunts and valvular regurgitation as demonstrated by angiocardiography. The results demonstrate a significant decrease in ventricular compliance in patients with coronary heart disease. The relationship of this finding to ventricular function is discussed.

Notes: Summary The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 × 4 g Colestyramin), and diet counselling. Male patients, average age 48 (≤ 56) years, were included with angiographic CAD and a screening total cholesterol of 207–350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, wh did not suffer from serious other disease (e.g., diabetes mellituss), and who had not undergone coronary bypass surgery previously. Results: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of −35%, in Apo-Protein B (ApoB) of −30%, in VLDL-C of −37%, and in triglycerides (TG) of −27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: −41, −36, −39, −31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by −0.017; P: −0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: −0.20; P: +0.23 mm; P = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to fourtimes less in the S group as compared to the control group (S: by 0.69%; P: by 2.73 %; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; P 〈 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis “as treated”. The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronouncedf in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12–56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C group (n.s.), and so did the number of patients with any major adverse event and the absolute number of such events as well as the number of patients with minor adverse experiences and with minor laboratory deviations. Conclusion: In young men, on otherwise full CAD treatment, additional medication with 37 mg simvastatin daily for an average of 2.3 years slowed down angiographic progression of CAD significantly, with a predominant beneficial effect on medium sized coronary lesions. This emerged from the visual as well as the quantitative coronary analysis which gave equivalent and complementing results. By multivariate regression analysis, the inhibitory effect on progression is correlated to the considerable and highly significant difference in LDL-C (or ApoB) and TG effected by simvastatin in comparison to placebo according to the regression equation: ΔMOD [mm] = −0.109 + 0.0003 [TG mg/dl] + 0.0008 [LDL-C mg/dl].

Notes: Summary The surviving myocardium of the cat was studied 7 days and 6 weeks following experimental infarction. Seven days after infarction, ultrastructural alterations of the mitochondria indicative of slight hypoxic injury—clearing of the matrix and loss of dense matrix granules-were found. Together with intracellular edema and glycogen depletion this result was considered as a sign of relative hypoxia in the surviving myocardium 7 days after infarction. At the same time β-glucuronidase activity of tissue homogennates was found to be elevated. Focal ischemic lesions in remote myocardium which have been described by other authors (5, 6, 23) were not detected in our experiments. Six weeks after infarction, the fractional volume occupied by myofibrils had increased whereas the fractional volume of mitochondria had remained unchanged (left ventricle) resp. had decreased (right ventricle). There were no qualitative changes detectable at the ultrastructural level. Based on the morphometric investigation of Anversa (1, 2), our results were regarded indicative of mild compensatory hypertrophy of the surviving myocardium. Glutamate dehydrogenase activity of tissue homogenates was shown to be increased when compared to control values. Furthermore our morphometric results showed that the unit mass of mitochondria has to render an enhanced amount of energy six weeks after infarction which might leave the surviving myocardium with a higher susceptibility to future hypoxic injury.