Heart transplantation 248 Subject

McLeod HL, Lin J-S, Scott EP, Pui C-H, Evans WE. Thiopurine methyltransferase activity in American white subjects and black subjects. Clin Pharmacol Ther 1994 55 15-20. McLeod HL, Miller DR, Evans WE. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993 1341 1151. 

The finding that the administration of 6-mercaptopurine to rabbits following exposure to bovine serum albumin prevented antibody formation [374] formed the basis for a new area of chemotherapy for purine analogues and other antimetabolites and was soon followed by the use of these drugs for the therapy of autoimmune disease and the suppression of homograft rejection. This subject has been reviewed in depth [ 12, 375, 375a], has occasioned a symposium [376], and has received much recent publicity as a result of human heart transplants. 

A pure alpha agonist will cause reflex bradycardia in a subject with intact cardiac innervation, but no change in hean rate if this innervation is severed, eg, in a heart transplant patient. The other drugs listed have direct beta agonist effects and will increase heart rate in the denervated heart. The answer is (D). 

Serum MMP-3 and TIMP-2 were reported to be significantly higher in heart transplant recipients than in control subjects. The increase in MMP-3 is consistent with an inflammatory response in transplant recipients (D3). 

Famotidine is reported not to affect cielosporin blood levels. " However, higher eielosporin blood levels were found in a study of heart transplant patients given famotidine. No significant changes in the pharmacoldnet-ies of eielosporin was seen in a single-dose study in 8 healthy subjects and no changes in serum ereatinine or BUN levels were seen in 7 kidney transplant patients."... 

Fig. 3. Prevalence of atherosclerosis in coronary arteries of heart transplant recipients grouped by age [data taken from Tuzcu et al. (15), reproduced with permission]. Intravascular ultrasound was performed in 262 heart transplant recipients after transplantation to investigate coronary arteries in young asymptomatic subjects. Extensive imaging of all possible (including distal) coronary segments was performed, and 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. Sites with intimal thickness > 0.5 mm were defined as atherosclerotic. Prevalence of atherosclerosis varied from 1 7% in individuals < 20 y old to 85% in subjects > 50 y old. Overall prevalence of atherosclerosis was similar in men and women (52 and 51.7%, respectively).

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Hathaway TJ, Higenbottam TW, Morrison JF, Clelland CA, WaUwork J (1993) Effects of inhaled capsaicin in heart-lung transplant patients and asthmatic subjects. Am Rev Respir Dis 148 1233-1237... 

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