By Peter Laird, MD
Since going to the ADC last week and seeing the reports on myocardial stunning and on myocardial ischemia, I have entered a quest to see if there are any studies done on animal models that might explain these findings in the majority of hemodialysis patients. I wondered if there is a connection between the known pro-arrhythmic effects of low K dialysate as well as the known vasoconstriction effects of clinical hypokalemia that could be a causative factor in myocardial ischemia.
Interestingly, two recent nephrology blogs posted on the dangers of hypokalemia as well. (Precious Bodily Fluids, Uremic Frost) However, I had not been able to find any direct studies that would show local hypokalemia producing significant coronary artery vasoconstriction that could be a contributing factor in the ubiquitous myocardial ischemia found in dialysis patients.
After looking through hundreds of articles, I finally came across an article from 1974 that actually demonstrated that exact effect. In addition to coronary vasoconstriction from artificial local hypokalemia, the low potassium infusion also increased myocardial contractions which in the setting of coronary vasoconstriction would also increase myocardial oxygen demand that could lead to ischemia.
Lastly, the same study noted a considerable reduction in oxygenation in the coronary sinus. The issue of myocardial ischemia and myocardial stunning in dialysis patients needs immediate attention beyond the meager studies to date. I believe that we have a basis to conduct further studies in animal models looking directly at the etiology of dialysis related myocardial ischemia in an expeditious manner and whether the method of removing potassium plays a role. My life and thousands of others are at risk today:
AMERICAN JOURNAL OF PHYSIOLOGY
Vol. 227, No. 3, September 1974. Printed in U.S.A.
Local effects of hypokalemia on coronary resistance and myocardial contractile force
ROBERT A. BRACE, DONALD K. ANDERSON, WANG-TSAU CHEN, JERRY B. SCOTT,
AND FRANCIS J. HADDY
Departments of Physiology and Chemical Engineering,
Michigan State University,
East Lansing, Michigan 4882Discussion:
It is evident from these experiments that acute local hypokalemia produces dramatic effects on both coronary blood vessels and myocardial cells. During constant-flow or constant-pressure perfusion of the left common coronary artery, both ventricular contractile force and coronary vascular resistance increased greatly and, with constant- pressure perfusion, coronary sinus oxygen tension decreased significantly during the first few minutes of hypokalemic perfusion. The initial increase in resistance to blood flow seen during the constant-pressure perfusion waned with time and actually became less than the control resistance, even though contractile force remained elevated.
The increases in coronary vascular resistance seen during local hypokalemia may result from both passive and active vasoconstriction. The mechanical effect of increased contractile force might increase resistance to flow by passively reducing vessel caliber. While it is difficult to assess whether the increase in resistance is due to active or passive vasoconstriction, we have shown in previous experiments (2, 10) that hypokalemic perfusion of the canine gracilis muscle also increases vascular resistance to blood flow. In those experiments, there was no comparable mechanical effect such as that produced by the beating heart. More likely, most of the increase in coronary vascular resistance is produced by an active mechanism elicited by the changes in [K+]. We have hypothesized (2, 10) that hypokalemia increases resistance to blood flow in skeletal muscle by inhibition of the membrane Na-K+-ATPase and slowing of the electrogenic pump in the vascular smooth muscle. This leads to depolarization of the smooth muscle cells and thus active vasoconstriction.
Understanding that local hypokalemia constricts coronary blood flow and increases oxygen demand at the same time presents a potential area of intervention that may significantly reduce the prevailing risks of sudden cardiac death if the same phenomenon is shown in patients on hemodialysis. To date, the causative factors for increased sudden cardiac death have defied definition in the dialysis population. Certainly the known arrhythmogenic effects of low potassium dialysate baths documents a physiologic and dose related effect of dialysate potassium concentrations.
This 1974 physiology study on the effect of low potassium concentrations directly on the coronary arteries is an intriguing and interesting putative causation of the well documented myocardial ischemia and myocardial stunning seen in dialysis patients. Since low potassium dialysate has electrocardiographic effects on the heart, and low potassium has coronary vasoconstrictive effects and increases the oxygen demand, is it possible that low potassium dialysate also has a vasoconstrictive effect that could cause myocardial ischemia in the usual dialysis setting? I believe it is a question that demands an immediate verdict.
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