Protection of ischemic myocardium by inhibition of contracture in isolated rat heart.

Protection of the ischemic myocardium by pretreatment with a high dose of 2,3-butanedione monoxime (BDM) is attributed to the enhancement of glycolytic ATP production rather than to the inhibition of contracture during mild ischemia. Our objective was to investigate whether the inhibition of contracture would protect the arrested heart during prolonged ischemia. Isolated perfused rat hearts were subjected to 30 min of low-flow ischemia followed by reperfusion. Ischemic hearts were treated with BDM (5 mmol/l) after beating stopped. BDM ameliorated the increase in intraventricular pressure after ischemia without significant changes in ATP levels and with a decreased accumulation of lactate. BDM treatment accelerated the recovery of function and high-energy phosphates with reduced myocardial Ca2+ overload. The results of this study suggested that inhibition of contracture can protect the heart from ischemia-reperfusion injury.

Intra-arterial administration of the angiogenesis inhibitor TNP-470 blocks liver metastasis in a rabbit model.

We evaluated the best route of administration of TNP-470, an angiogenesis inhibitor, by comparing the anti-tumour effects and toxicity following injection via the hepatic artery, the portal vein, or the jugular vein in a rabbit model of liver metastases. Following the injections of 1 x 10(6) VX2 carcinoma cells into the portal vein of rabbits, 50 mg of TNP-470 was injected continuously into the hepatic artery, portal vein, or jugular vein for 7 days. The number of tumours on the surface of the liver was counted 14 days following the start of the infusion, and the serum glutamic-oxaloacetic transamine (GOT), glutamic-pyruvic transaminase (GPT) and total bilirubin concentrations were examined. In addition, a coloured silicon rubber was injected into the vessels of the liver to visualise the capillary networks around the tumours and assess the degree of suppression of angiogenesis by TNP-470. The mean number of tumours following intra-arterial injection (17.5 +/- 2.9) was significantly less than the control (237.0 +/- 34.0) (P < 0.05). The mean numbers of the tumours following intraportal (89.1 +/- 16.0) and intravenous (140.6 +/- 31.2) injection were both less than the controls (215.3 +/- 45.5, 284.8 +/- 55.4 respectively), but the differences were not significant. We conclude that intra-arterial injection of TNP-470 is the most effective method for preventing liver metastases in this model.