Cardiac beta-adrenoceptors and the positive inotropic effects of adenylate cyclase-dependent (dobutamine, histamine, forskolin) and adenylate cyclase-independent agents (isobutylmethylxanthine (IBMX), dibutyryl-cAMP (db-cAMP), digoxin, digitoxin and calcium were measured in papillary muscle strips from severely failing (NYHA IV), moderately failing (NYHA II-III) and non-failing (NYHA I) human hearts. The density of beta-adrenoceptors in three NYHA I patients were 40.0, 42.0 and 42.9 fmol mg-1 protein. The density of cardiac beta-adrenoceptors was significantly reduced in NYHA II-III to 18.0 +/- 1.1 fmol mg-1 protein (n = 16) and further reduced in NYHA IV to 9.5 +/- 1.6 fmol mg-1 protein (n = 7). The KD values did not differ between the groups. Correspondingly, the positive inotropic effect of dobutamine was significantly reduced in NYHA II-III and almost lost in NYHA IV. The positive inotropic effect of histamine was similar in non-failing and moderately failing myocardium but reduced in preparations from severely failing hearts (NYHA IV). The positive inotropic effect of IBMX was diminished in moderately and severely failing myocardium depending on the functional class of heart failure. In contrast, the effects of forskolin, db-cAMP, digoxin and digitoxin were not impaired in NYHA IV when compared with the maximal positive inotropic effect of calcium. It is concluded that in the failing human heart (a) the number of cardiac beta-adrenoceptors is reduced proportional to the severity of heart failure; (b) the receptor coupling of H2-receptors to adenylate cyclase may be impaired, but only in severe heart failure; (c) the basal cAMP formation may be diminished; and that (d) the catalytic subunit of the adenylate cyclase and the cAMP-dependent protein kinases may be promising targets for drugs to restore force of contraction in human heart failure.

The frequently observed de-endothelialization of venous coronary bypass grafts prepared using standard methods exposes subendothelial prothrombotic cells to blood components, thus endangering patients by inducing acute thromboembolic infarction or long-term proliferative stenosis. Our aim was to gain deeper histological and physiological insight into these relations. An intricate network of subendothelial cells, characterized by histological features specific for true pericytes, was detected even in healthy vessels and forms, coupled to the luminal endothelium, a second leaflet of the macrovascular intima. These cells, and particularly those in the venous intima, express enormous concentrations of tissue factor and can recruit additional amounts of up to the 25-fold concentration within 1 h during preincubation with serum (intimal pericytes of venous origin activate 30.71 ± 4.07 pmol coagulation factor x·min−1·10−6 cells; n = 15). Moreover, decoupled from the endothelium, they proliferate rapidly (generation time, 15 ± 2.1 h, n = 8). Central regions of atherosclerotic plaques, as well as of those of restenosed areas of coronary vein grafts, consist almost completely of these cells. In stark contrast with the prothrombogenicity of the intimal pericytes, intact luminal endothelium recruits high concentrations of thrombomodulin (CD 141) specifically within its intercellular junctions, activates Protein C rapidly (42 ± 5.1 pmol/min·106 venous endothelial cells at thrombin saturation; n = 15), can thus actively prevent coagulatory processes, and never expresses histologically detectable and functionally active tissue factor. Given this strongly prothrombotic potential of the intimal pericytes and their overshooting growth behavior in endothelium-denuded vascular regions, they may play important roles in the development of atherosclerosis, thrombosis, and saphenous vein graft disease.

CABG using both ITAs can be performed routinely with good clinical results and low mortality. Compared with single ITA grafting, sternal and bleeding complications were slightly increased. Diabetes mellitus, BITA grafting, duration of surgery but not obesity or COPD could be identified as independent risk factors for sternal complications. Dialysis-dependent renal failure, EF<30%, emergent cases, and the absence of BITA grafting were predictors for increased perioperative mortality.

Acute mesenteric ischemia is a rare but severe complication after open heart surgery. Its incidence (0.2-0.4%) is quite low, but mortality rates are ranging between 70% and 100%. From October 1992 to December 1996, 4,640 patients underwent open heart surgery with cardiopulmonary bypass: 74.6% coronary artery bypass graft (CABG) operations, 23.2% valve replacement including aortic repairs, and 2.2% corrections of congenital heart diseases or tumors of the heart. The overall mortality rate (30 days) was 3.4%, and after CABG, 2.9%. Twelve patients (0.26%), following CABG (one combined with aortic valve replacement, one with mitral reconstruction, and one with carotid disobliteration) developed signs of acute mesenteric ischemia in the early postoperative period (day 1 to 5). In all patients various abdominal symptoms, leukocytosis, acidosis, hyperlactatemia, hyperosmolality, renal failure, and, finally, hemodynamic instability were observed. Eleven patients underwent emergency laparotomy. Mesenteric angiography was done if possible in still stable patients (n=7); it showed severe stenosis or occlusion prior to the operation in each case. Other diagnostic methods were not reliable. In six patients (55%) during the first look, extensive bowel necrosis was found and in five patients an ischemic intestine but no necrosis was detected. Of these, three patients were affected by extensive bowel gangrene at the second look. In the fourth patient a disseminated peripheral ischemia of the entire small intestine was found intraoperatively. After mechanical release and stimulation normal bowel function could be reestablished. One patient underwent percutaneous transluminal angioplasty prior to the laparotomy. Bowel perfusion was still deteriorated but no necrosis was found intraoperatively. These patients were the only survivors in the investigated group; 10 of 12 patients (83.3%) died in the early postoperative period (day 1 to day 6). Predisposing factors for mesenteric ischemia are: arteriosclerotic patients after CABG (100%), age >70 years (91.7%), hyperosmotic dehydration (100%), and cardiac ischemia in 25%. Mesenteric ischemia is a fatal complication with high mortality rates after open heart surgery, especially in older, dehydrated patients with generalized atherosclerotic vessel disease. As the acute mesenteric ischemia usually starts during anesthesia or in the early postoperative period, setting of immediate diagnosis is very difficult. With the occurrence of typical symptoms diagnostic and therapeutic procedures (angiography and laparotomy) must be done very urgently owing to the life-threatening mesenteric process. When mesenteric gangrene already has taken place, the prognosis is very poor, despite extensive resection. Prevention can be exercised by avoiding perioperative hyperosmotic dehydration of patients at high risk.

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