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Bone marrow cells are used for cell therapy after myocardial infarction (MI) with promising results. However, cardiac persistence of transplanted cells is rather low. Here, we investigated strategies to increase the survival and cardiac persistence of mononuclear (MNC) and mesenchymal (MSC) bone marrow cells transplanted into infarcted rat hearts. MNC and MSC (male Fischer 344 rats) were treated with different doses of PDGF-BB prior to intramyocardial injection into border zone of MI (syngeneic females, permanent LAD ligation) and hearts were harvested after 5 days and 3 weeks. In additional experiments, untreated MNC and MSC were injected immediately after permanent or temporary LAD ligation and hearts were harvested after 48 h, 5 days, 3 weeks, and 6 weeks. DNA of the hearts was isolated and the number of donor cells was determined by quantitative real-time PCR with Y chromosome-specific primers. There was a remarkable though not statistically significant (p = 0.08) cell loss of approximately 46% between 5 days and 3 weeks in the control group, which was completely inhibited by treatment with high dose of PDGF-BB. Forty-eight hours after reperfusion only 10% of injected MSC or 1% for MNC were found in the heart, decreasing to 1% for MSC and 0.5% for MNC after 6 weeks. These numbers were lower than after permanent LAD ligation for both MNC and MSC at all time points studied. Treatment with PDGF-BB seems to prevent loss of transplanted bone marrow cells at later times presumably by inhibition of apoptosis, while reperfusion of the occluded artery enhances cell loss at early times putatively due to enhanced early wash-out. Further investigations are needed to substantially improve the persistence and survival of grafted bone marrow cells in infarcted rat hearts, in order to fully explore the therapeutic potential of this novel treatment modality for myocardial repair.

Bone marrow cells are used with promising results for cell therapy after myocardial infarction (MI). We determined the survival and organ distribution of transplanted mononuclear (MNC) or mesenchymal (MSC) bone marrow cells, and the influence of cell type, cell number and application time. MNC and MSC (male Fischer 344 rats) were injected into the border zone of MI (syngeneic females) immediately or 7 days after LAD ligation (10(5) or 10(6) cells, 50 microl). After 0 h, 48 h, 5 days, 3 weeks and 6 weeks, DNA of heart, lung, liver, spleen, kidney, blood, bone marrow, brain and skeletal muscle was isolated and the number of donor cells determined by quantitative real-time PCR with Y-chromosome specific primers (each n>or=4). The percentage of donor-cells in the heart decreased rapidly from 34-80% of injected cells (0 h) to 0.3-3.5% (6 weeks) independent from cell type, number and application time. The absolute number increased after increasing injected cell number (10(6) vs. 10(5)). In the lung, MNC and MSC were found at 0 h (126+/-48 and 140+/-3 per million organ cells), but in liver and kidney, only few. At 48 h and 6 weeks, an increasing number of MNC, but not MSC, were detected in the spleen (6 weeks, 602+/-173 per million organ cells vs. 95+/-50 in the heart, P=0.02). In all other organs, only few or no grafted cells of either cell type were detected at these times. Organ distribution was independent from injection time. The low survival of grafted cells may limit their therapeutic impact, while their distribution to other organs must be considered in all cell therapy applications.

We have investigated the possible contribution of an early capillaropathy to the increased incidence of myocardial infarction (MI) in patients who had impaired glucose tolerance (IGT) during an i.v. glucose tolerance test (IVGTT). In lieu of the myocardium, biopsies from the quadriceps femoris muscle were studied for muscle capillary basement membrane (MCBM) thickening. Fluorescence angiography was performed to detect capillary retinopathy. Plasma growth hormone (GH) concentrations were determined during IGT. Data were obtained from 14 male patients with MI and IGT on IVGTT. Nine healthy subjects served as controls. MCBM thickness was similar in patients and controls (1,107 +/- 55 vs 1,067 +/- 88 A). None of the patients had signs of capillary retinopathy, and plasma GH concentrations were not higher in the patients as compared to control subjects. It is concluded that, in patients with IGT on IVGTT, MCBM thickening is probably not a factor for the development of MI.

In 85 patients with myocardial infarction undergoing a physical training on a bicycle ergometer 3 times a week over a period of 18 months beginning 5 weeks after the acute infarction, telemetric and haemodynamic investigations were made. The telemetry was done during ergometer training, dynamic and isometric gymnastics and during work at home. The diastolic pulmonary arterial pressure under exercise was registered in 43 patients before the beginning of the training program; in 16 of these patients a control heart catheterization was made after a training period of 4 months. During the ergometer training program 32% of all patients had ventricular premature beats more than 1:10, 6% had paroxysmal ventricular tachycardias, 1 patient had supraventricular tachycardias and 1 patient died at home after having a tachycardia of unknown origin. During dynamic or isometric gymnastics or under work at home the patients had not more arrhythmias than in the telemetric controls during the ergometer training. Arrhythmias and other complications are very often found in patients with high diastolic pulmonary arterial pressure in the exercise test.

The hemodynamic effects of nitroglycerin and nifedipin and the application of both substances during a long term training program in patients with angina pectoris, myocardial infarction, and myocardial dysfunction (=48) were studied. Cardiac output, heart rate, and arterial blood pressure showed no significant changes after application of nitroglycerin and nifedipin. After nitroglycerin, however, there were significant drops of pulmonary arterial pressure and right atrial pressure during rest and exercise, whereas no changes were seen after nifedipin. With the application of nitroglycerin (but not with nifedipin) prior to the daily physical training program on a bicycle ergometer, all patients with angina pectoris and myocardial dysfunction showed an increasing training effect during the long term program and their angina pectoris improved.