THE ACUTE EFFECT OF MINOCYCLINE ON THE PERICARDIUM - EXPERIMENTAL ANDCLINICAL FINDINGS

Study objectives: To evaluate the acute effect of minocycline on the p ericardium in the experimental animal and in the human with malignant pericardial disease. Design: A prospective study in open-chest dogs an d in humans. Setting: Experimental surgery laboratory, medical school; coronary care unit, university hospital. Methods: Twenty-three open-c hest dogs were divided into four groups according to the solution inje cted intrapericardially: (1) minocycline, 5 mg/kg; (2) minocycline, 10 mg/kg; (3) normal saline solution, 100 mt, followed by minocycline, 1 0 mg/kg; (4) a mixture of 50 mt of the dog's own blood mixed ex vivo w ith minocycline, 10 mg/kg to evaluate the effect of rising pH of minoc ycline solution. The extent of myocardial injury is evaluated by measu ring ST-T segment deviation in six standard bipolar leads and in three unipolar electrograms recorded over the left ventricular pericardial surface. The pH of the various minocycline solutions is measured. Nine consecutive patients with malignant cardiac tamponade receiving minoc ycline intrapericardially are evaluated for the appearance of chest pa in and ECG changes. Results: Minocycline (5 and 10 mg/kg) caused marke d, transient ST-T segment deviation in all dogs, whether or not saline solution was previously injected into the pericardial sac. Prior mixi ng of minocycline with blood markedly increased the acidic pH of the m inocycline solution and significantly reduced the extent of ST-T segme nt deviation. Four of nine patients had chest pain during minocycline injection. None had ST-T segment changes. Conclusion: Minocycline caus es a marked, transient injury to the epicardial-pericardial surface. O ur animal and in vitro studies indicate that this acute injury is prob ably partly related to the acidic pH of the minocycline solution. Our experimental findings suggest that this minocycline-induced injury may be reduced by raising the pH of the solution either ex vivo (eg, by m ixing minocycline with previously withdrawn pericardial fluid) or in v ivo (eg, by leaving 200 to 300 mL of pericardial fluid prior to minocy cline injection). Limited experience in the human with malignant cardi ac tamponade indicates that intrapericardial minocycline is usually we ll tolerated, although severe chest pain may appear.