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Objectives: Induction of the 70 kd heat shock protein in the heart is known to exert a protective effect against postischemic mechanical and endothelial dysfunction. However, the exact site of induction and the mechanisms involved remain unknown. The aim of this study was to investigate the relative capacity of endothelial and myocardial cells to express the 70 kd heat shock protein in response to heat stress, as well as their significance.Methods: (1) Postischemic recovery of cardiac mechanical and endothelial function was studied in isolated rat hearts with and without endothelial denudation with saponin. (2) Semiquantitative determination of induction of 70 kd heat shock protein by Western immunoblotting was performed in the whole cardiac homogenate, in isolated cardiac myocytes, and in coronary endothelial cells. (3) Immunocytochemistry was used to visualize the distribution of induction of 70 kd heat shock protein in both cell types.Results: Postischemic recovery (percent preischemic value ± standard error of the mean) of cardiac output in hearts from heat-stressed animals was significantly improved (66.7 ± 6.9 vs 44.5 ± 4.5 in the control group, p < 0.01). In heat-stressed hearts treated with saponin no improvement in the recovery of cardiac output was noted (44.7 ± 6.9 in heat-stressed hearts vs 38.0 ± 4.0 in heat-stressed, saponin-treated hearts, p = not significant). Endothelial function (as assessed by the vasodilatory response to the endothelium-dependent vasodilator 5-hydroxytryptamine) improved from 31.0 ± 5.2 in the control group to 65.8 ± 7.1 in heat-stressed hearts (p < 0.02 vs control) and dropped to –1.9 ± 3.8 in heat-stressed hearts treated with saponin. Immunocytochemistry showed that only sections of hearts from heat-treated rats showed a strong specific reaction with heat shock protein antibody. The positive staining was seen in endothelial cells. Induction of 70 kd heat shock protein content in the whole cardiac homogenate from heat-stressed rats as measured by Western immunoblotting was 5.2 ± 1.9 (vs 0.0 in non-heat–stressed rats, p < 0.0001) and dropped to 0.0 in heat-stressed hearts treated with saponin. The tentative amount of 70 kd heat shock protein was 18.1 ± 7.8 in isolated endothelial cells from heat-stressed hearts and 2.3 ± 2.3 in isolated cardiac myocytes ( p < 0.01 vs endothelial cells).Conclusions: Coronary endothelial cells are the main site of induction of 70 kd heat shock protein in the heart and appear to contribute to the protective effects of heat stress on the recovery of mechanical and endothelial function. (J Thorac Cardiovasc Surg 1998;115:200–9)

Objective: Endothelin-1 (ET) is a potent endogenous vasoconstrictor which has been shown to be increased following ischaemia and cardiopulmonary bypass. We tested the hypothesis that inhibition of ET synthesis during cardioplegic arrest using phosphoramidon (an ET converting enzyme inhibitor) or blockade of ET receptors using bosentan (a mixed ETA:ETB antagonist), might improve the postischaemic recovery of coronary flow. Methods: Using an isolated Langendorff perfused rat heart model we compared the addition of phosphoramidon or bosentan to St Thomas’ Hospital No.1 cardioplegia vs. control (plain cardioplegia). We measured recovery of coronary flow followin g4ho fcardioplegic arrest at 4°C. In a second series of experiments using an isolated working rat heart model we measured the recovery of cardiac function followin g4ho fcardioplegic arrest at 4°C. Results are expressed as percentages of preischaemic values (9 S.E.M). Results: In the first series of experiments, addition of phosphoramidon to cardioplegia improved the postischaemic recovery of coronary flow after 30 min of reperfusion: control 81.3% (93.5); phosphoramidon 10 6 M 86.2% (93.1); phosphoramidon 10 5 M 95.0% (9 3.0) P 0.03 vs. control. Likewise, addition of bosentan 10 5 M improved coronary flow following 20 min of reperfusion: control 96.7% (9 4.0), and bosentan 109.6% (94.7) P0.04. The addition of phosphoramidon or bosentan had no effect on the postischaemic recovery of mechanical function following 30 min of reperfusion. Conclusion: Both inhibition of ET synthesis and ET receptor blockade during prolonged hypothermic arrest improves postischaemic coronary flow, but appears to have no effect on the recovery of cardiac mechanical function. © 1997 Elsevier Science B.V.

The ageing process is known to be associated with biochemical and functional changes in the heart. In an attempt to determine whether the ability of the coronary endothelium to secrete nitric oxide (NO) both at rest and in response to pharmacological stimulation is age dependent, we studied four groups of rats of different ages (1, 5, 15 and 26 months, respectively). Basal release of NO by endothelium as assessed by response of coronary flow to L-monomethylarginine, an inhibitor of NO synthase, was higher in the younger age groups. Similarly, the response of coronary flow to 5-hydroxytryptamine, a selective probe of endothelial capacity to secrete NO, was diminished in the older animals. This was confirmed by direct measurement of NO by chemiluminescence in the coronary effluent. In contrast, the response to glyceryl trinitrate appeared to be unaltered by age. It is concluded that in rats, basal and stimulated release of nitric oxide by the coronary endothelium deteriorates with age.

A 65-year-old woman presented with acute central chest pain. Her ECG showed inferior ST elevation and she was transferred to our cardiac catheterisation laboratory for primary percutaneous coronary intervention. Coronary angiography showed no obstructive coronary atheroma, though a foreign body appeared to be lodged within the heart (panel A). The following morning her troponin T level was raised at 1.15 ng/ml. A Port-O-Cath had previously been inserted via the right subclavian vein as part of the treatment of breast carcinoma. Thoracic CT demonstrated a fragment of the catheter lying across the fossa ovalis. There was no evidence of pulmonary thromboembolism or recurrence of the breast carcinoma. Transoesophageal echocardiography suggested thrombus was adherent to the fragment within the right atrium. After 1 weeks treatment with heparin, thrombus was still visible. As we considered percutaneous retrieval might cause systemic embolism, the fragment was removed under direct visualisation through a longitudinal right atriotomy while the patient was on cardiopulmonary bypass (panel B). At operation, most of the catheter fragment was seen within the left atrium without any visible thrombus attached; the patent foramen ovale was repaired and the remainder of the Port-O-Cath removed. The patient has remained asymptomatic. Catheter fracture usually results from compression of implanted catheters lying between the first rib and the clavicle. We suspect that the acute presentation was secondary to paradoxical thromboembolism to the coronary circulation. As far as we know, this is the first report of migration of a fractured venous catheter across a patent foramen ovale resulting in acute myocardial infarction. Coronary angiogram: right anterior oblique projection demonstrating the embolised venous catheter fragment within the atria. Hub port and catheter after removal; centimetre scale rule for reference.

Number of metabolic processes in the heart such as calcium handling or nucleotide metabolism, are known to be modified during ageing.1–3 Although several studies have evaluated the effect of differences in nucleotide metabolism of on the recovery of the heart after normothermic ischemia, little is known about its relationship with cardiac function after cardioplegic arrest and hypothermic ischemia, mimicking preservation for cardiac transplantation. In this study, we evaluated the association between concentration of purine nucleotides and functional recovery of the rat heart at different ages, after cardioplegic arrest and hypothermic ischemia.