Species variation in the coronary collateral circulation during regional myocardial ischaemia: a critical determinant of the rate of evolution and extent of myocardial infarction.

Abstract

There are several ‘villains’ in this story: (i) researchers who convinced themselves that myocytes could stay alive without blood; (ii) authors who discarded (or journal editors who refused to publish) negative studies; (iii) dogs that had too much and too variable a collateral flow; (iv) legislation and animal suppliers that made the use of canine preparations (and an intriguing alternative, see Fig. 1) impossible or prohibitively expensive; and (v) a UK government plot to exterminate the coypu (nutria). Fig. 1 Myocastor coypus molina (known as the coypu or nutria). A giant rat-like beast about 60 cm long and weighting up to 9 kg. Photo: courtesy of Michael Haramis of the Maryland Department of Natural Resources. For anyone interested in myocardial injury and protection, the 1970s and 1980s were both confusing and exciting. Almost every copy of every journal contained a new paper in which yet another drug reduced infarct size in a canine model of coronary artery occlusion and myocardial infarction. The interventions ranged from the well known (beta blockers, calcium antagonists, vasodilators and glucose) through the surprising and sometimes disasterous (steroids) to the bizarre (rutosides, cobra venom and hyaluronidase). Opinion leaders in the field vigorously promoted the concept that just because myocardial tissue lay within the distribution of a recently occluded coronary artery did not mean that it was necessarily condemned to death — despite the absence of reperfusion. For those of us who believed that early reperfusion was an absolute prerequisite for the salvage of severely ischemic tissue this seemed like heresy! Astounding claims resounded from the dog labs but, despite this, clinical trials were consistently disappointing and no single intervention was ever adopted for widespread clinical use as an anti-infarct agent in patients with myocardial infarction. Clearly, something was wrong — possibly the design of the trials, the choice …