Vulnerable myocardium

Mid-ventricular takotsubo syndrome (see also p. 313) has also been described in a 75-year-old woman taking anagrelide [139" ]. The authors hypothesized that accumulation of anagrelide, a phosphodiesterase type II inhibitor, had caused major inotropic stimulation and sympathetic hyperactivation in a vulnerable myocardium. 

Diuretics and their mechanisms of action will be discussed in detail in Chapter 21. Loop diuretics, such as furosemide (Lasix), block the Na" -K" -2CLsymporter in the ascending limb of the loop of Henle.The resultant effect is delivery of more Na" to the distal tubule and enhanced urinary loss of Na" and water. Unfortunately, the resultant increase in urinary excretion of and K+ can lead to arrhythmias. The potential for arrhythmias is exacerbated by the loss of Mg++ and Ca++ and an underlying vulnerability of the myocardium in CHF. However, loop diuretics are still part of the mainstay of therapy for CHF despite these potential problems and the absence of well-controlled multicenter clinical trials. The rationale for their use is so compelling that placebo-controlled studies appear unethical. Moreover, furosemide was accepted as the standard of care in all of the clinical trials that form the basis for recommended therapy for CHF. The use of the potassiumsparing diuretic spironolactone has been shown to improve survival and is discussed below. 

Tricyclic antidepressants are highly concentrated in the myocardium this may account for the vulnerability of the... 

Ischemic heart disease coexists with certain illnesses which may potentially influence the response of the myocardium to ischemia. Experimental evidence shows that the diseased myocardium may be either vulnerable or tolerant to ischemia and reperfusion injury. Much of the controversy could be attributed to differences in the experimental design, such as the duration and severity of the disease or the severity of the ischemic insult. The response of the myocardium to ischemia seems to vary with age. 

J.M. Canty, G. Suzuki Jr, M.D. Banas, F. Verheyen, M. Borgers J.A. Fallavollita, Hibernating myocardium chronically adapted to ischemia but vulnerable to sudden death, Circ. Res. 94,507-516 (2004). 

Lastly, it is now recognized that the diseased myocardium can adapt to ischemic stress and is not always a vulnerable substrate to ischemia. 

Myocardial ischaemia is the name given to the decrease in the perfusion of a certain area of the myocardium. Therefore whenever the oxygen supply is not sufficient for demands, a state of myocardial ischaemia occurs. This may be caused by (1) acute diminution of a coronary blood flow (ACSs and MI), which is usually secondary to the complete or partial occlusion of a coronary artery due to atherothrombosis, and (2) when there is an increase of a myocardial oxygen demands. The latter happens with exercise in cases in which impaired myocardial perfusion already exists, especially in the subendocardium when the coronary arteries have a diminished ability to increase a coronary blood flow (exercise angina). We have to remind that the subendocardium is more vulnerable to myocardial ischaemia because its vasodilatory capacity is less, and this vulnerability increases during exercise (tachycardia) (see p. 57). 

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