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Singh et al. Myocardial protection in cardiac transplantation

experiments. Cardiovascular function remained stable death. Papadopoulos et al. [119] found that vasopressin
in both control and experimental vasopressin-infusion administration reduced the dose of requirements of
groups, with the only significant difference being a catecholamines and contributed to prevention of the
moderate rise in pulmonary artery pressure. post-cardiotomy vasoplegic shock in the patient with
low ejection fraction (30-40%) on ACE inhibitors in a
Rostron et al. [115] conducted a similar study looking double blind randomized controlled trial whereby the
at the effects of arginine vasopressin in preventing group A who were infused with low dose vasopressin
neurogenic vasoplegia which exacerbates lung injury. and the group B who were infused with normal saline
They induced brain death in Wistar rats by inflating an intraoperatively and for the 4 post-operative hours.
intracranial balloon mimicking coning. They noted an This further illustrated the benefits of vasopressin out
increment in pulmonary capillary permeability, wet/dry with the correction of neurogenic diabetes insipidus.
lung weight ratios, neutrophil integrin expression and
pro-inflammatory cytokines in serum (TNF-α, IL-1β, Glucose-Insulin-Potassium
CINC-1 and CINC-3), bronchoalveolar lavage (TNF-α, Calva et al. [120] first conducted experiments on canines
IL-1β,) and lung tissue (IL-1β and CINC-1) in braindead by inducing myocardial infarctions via coronary artery
animals compared to controls. These effects were ligation noting the extent of damage to the mitochondria
corrected by administration of arginine vasopressin with and without glucose-insulin-potassium regimes in
(AVP) and norepinephrine to correct the neurogenic the 60s. Opie et al. [121] conducted similar studies with
hypotension. baboons and noted similar findings, a reduction in
mitochondrial damage and decreased infarction and
Another study conducted by Chen et al. [116] investigated reduced ST segment depression on EKG. Multiple
vasopressin deficiency and hypersensitivity as a studies have since been done to study the effect
potential contributing factor to hypotension in organ of glucose-potassium-insulin (GKI) on myocyte
donors. In their cohort of 50 organ donors, 10 patients function. Human studies were first pioneered by
were treated with a continuous infusion of vasopressin Sodi-Pallares et al. [122] in which 10 patients with
(0.04 to 0.1 U/min). Mean arterial pressure (MAP), acute myocardial infarction and 20 patients with
catecholamine requirements, serum vasopressin, chronic coronary insufficiency, with 3 patients showing
and serum osmolality were obtained before and after improvements but 2 patients worsening and a general
vasopressin administration. An increment of MAP improvement in the chronic patients. A meta-analysis
allowed complete discontinuation of catecholamine however revealed no reduction in mortality in patients
pressors in 40% of patients and a decrement in receiving GKI in randomised studies [123] . They concluded
pressor dose in another 40%. Plasma vasopressin that while it may have had a potential benefit in the pre-
levels (2.9 ± 0.8 pg/mL) were notably low for the degree revascularisation and thrombolysis era, its benefits
of hypotension. It is likely that haemodynamically are not clearly evident now. Sun et al. [124] investigated
unstable organ donors may not only display diabetes the role of GKI for prevention of oxygen free radical
insipidus but also have a defect in baroreflex-mediated injury during reperfusion of ischaemic stored hearts.
secretion of vasopressin, for which supplementation Comparing known free radical scavengers (superoxide
would permit catecholamine sparing. The dismustase and catalase) alone and combination
catecholamine sparing effects of vasopressin were with GKI in rat models, they noted that there was no
also noted by Pennefather et al. [117] in which 24 DBD added benefit of GKI infusion in reduction reperfusion
donors were randomised to receive either saline or low injury once reperfusion was commenced, but noted
dose AVP. The AVP group had a decreased plasma an improvement in the superoxide dismustase and
hyperosmolality (P < 0.05), improved blood pressure catalase infusion group. A significant improvement
(P < 0.01), and reduced inotrope use (P < 0.01), while however was noted when GKI and the free radical
maintaining cardiac output. Myocardial ATP levels scavengers were combined showing improvement in
were higher in the AVP than the control group (NS). left ventricular end-diastolic pressure, myocardial blood
Kinoshita et al. [118] studied the effects of epinephrine flow. They concluded that free radical scavengers in
and arginine vasopressin in 10 brain dead patients. the presence of glucose-insulin-potassium significantly
Patients maintained haemodynamic stability for more improve functional recovery in the setting of heart
than a week with an initial rise in ST wave changes that transplantation.Myocardial dysfunction that occurs
was reversible. This was confirmed by a normal level post brain death is a phenomenon that is ubiquitously
of CK-MB and normal or slightly swollen mitochondria reported but not fully understood. It is thought to be
on cardiac biopsy specimens, highlighting the role related to direct myocardial injury from sympathetic
of both arginine vasopressin and epinephrine in activation [125] , potential reduction in oxidative
maintaining haemodynamic stability post brain metabolism from the reduction in T3, variability

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