Effect of propranolol and phentolamine on myocardial necrosis after subarachnoid haemorrhage.

Abstract

Summary and conclusions A study was set up to assess the effect on the clinical course of subarachnoid haemorrhage (SAH) of giving propranolol 80 mg eight-hourly plus phentolamine 20 mg three-hourly by mouth for three weeks. Out of the 90 patients studied, 14 died. Two of the deaths occurred in an open pilot study of 10 patients, the remaining 12 deaths occurring in patients in a randomised doubleblind placebo-controlled study. Postmortem examination was carried out on 12 of the patients, six of whom had been receiving placebo and six propranolol plus phentolamine. Necrotic myocardial lesions were present in the hearts of all six patients (age range 30-59 years) who died while taking placebo (all had had abnormal electrocardiograms (ECGs)). In contrast, no necrotic lesions were found in the hearts of the six patients (age range 28-59) who died while receiving the drugs (all had previously had normal ECGs).We conclude that the necrotic myocardial lesions were induced by catecholamines and that propranolol had a cardioprotective effect. While death from a further haemorrhage in cases of SAH is not affected by propranolol and phentolamine, propranolol may have a beneficial effect in other potentially lethal stresses.

Concurrent subarachnoid haemorrhage and myocardial injury

“…26 Furthermore, in both experimental and clinical intracerebral haemorrhage, cardiac damage is prevented by beta-adrenergic blockade. [27][28][29] The severity of the neurological insult (and therefore, the magnitude and duration of the catecholamine surge) may determine whether a patient develops myocardial damage. For example, in patients with SAH, poor neurological grade was associated with the presence of wall motion abnormalities.…”

Ogłuszone serce neurogenne — czy uwzględniamy to rozpoznanie u chorych z ostrym uszkodzeniem ośrodkowego układu nerwowego i niewydolnością serca?

“…Moreover, excessive contraction of sarcomeres and interstitial infiltration of lymphocytes and monocytes are observed. The histopathological lesions are most profoundly expressed subendocardially while the apex is relatively spared; their severity correlates with sympathetic innervation and not vasculature [27]. Another contributing factor to NSM may be excessive peripheral activity of the sympathetic system with increased concentrations of circulating catecholamines.…”

“…Excessive local stimulation of postsynaptic receptors causes the prolonged opening of b1 adrenergic receptor-dependent calcium channels [3,24]. This prolongs actin-myosin interactions resulting in the depletion of ATP stores and mitochondrial dysfunction [27]. Another consequence of calcium inflow to the cells is the release of free oxygen radicals and peroxidation of cell membranes, due to which some cardiomyocytes die.…”

“…The acute pathological process in the CNS results in an enhanced inflammatory response. Immunologically active mediators, including cytokines, adhesive molecules, biologically-active peptides and others, are produced in the brain and released into the systemic circulation [27]. This can initiate systemic inflammatory response syndrome (SIRS), leading to the dysfunction of many organs, including the heart [27].…”

“…subarachnoid haemorrhage or cerebral stroke) [3,27]. The acute pathological process in the CNS results in an enhanced inflammatory response.…”