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Cardiothoracic Surgery, Emory University, Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, 550 Peachtree St, NE, Atlanta, GA 30308-2225
(Email: jvinten{at}emory.edu).
Depolarizing the heart with hyperkalemic cardioplegia solutions arrests the heart but is associated with an on-going, albeit lowered, metabolic demand that requires either hypothermia or intermittent/continuous delivery to attenuate the consequences of this ongoing demand (ie, ischemia). However, simplicity, visibility, economy, and avoiding the consequences of systemic hyperkalemia would make a single delivery of hypothermic cardioplegia desirable, especially during aortic arch repairs and other complex procedures that require long arrest times.
Fannelop and colleagues [1] have compared physiologic outcomes of a single infusion of Custodiol HTK (Odyssey Pharmaceuticals Inc, East Hanover, NJ) crystalloid cardioplegia solution with a multidose strategy of cold blood cardioplegia in a swine model of cardiac arrest on cardiopulmonary bypass. Their hypothesis was equivalency of protection between the two modalities. The authors' interpretation of the data disproved their "null" hypothesis in favor of better myocardial protection with multidose cold blood cardioplegia.
However, the data are not so clear-cut as to be incontrovertible. The functional data suggest equivalence between the two formulations. The cardiac index was initially higher in the blood cardioplegia group, but this advantage was lost after 2 hours of reperfusion; the trajectory of the preload-recruitable stroke work index suggests that the advantage observed after 3 hours of reperfusion would be lost if the observation period were extended to 4 hours or more. There was no significant group difference in ejection fraction, end-systolic pressure-volume relation, or the relaxation variables 
or end-diastolic β modulus of stiffness. The most compelling data for superiority with multidose cardioplegia were (1) the troponin data which, at 3 hours, was 1/2 of that in the HTK group, and (2) the incidence of ventricular fibrillation, which was 6/8 in the HTK group and only 2/8 in the blood cardioplegia group.
The importance of the investigators' question demands further investigation, with perhaps different experimental designs: multiple doses of each solution should be tried; single doses of each formulation should also be investigated for a more balanced design and to allow valid comparisons. The cross-clamp time should be extended to more accurately reflect the complex cases for which the cardioprotective algorithm was tested; the period of reperfusion should be extended to at least 72 hours to go beyond the acute phase of recovery.
The larger question, however, may be whether hyperkalemia itself as a central component of depolarizing cardioplegia solutions can protect the heart under single-dose regimens. The induction of arrest and hypothermia do not stop metabolism entirely; indeed, residual metabolism related to ionic pump activity to counter ionic shifts uses energy that is ostensibly replenished only by intermittent or continuous delivery. Alternatively, locking the membrane potential at its resting state to prevent ionic shifts and reduce other "futile" expenditures of energy may be necessary to bring the single-shot concept into reality. Thinking out of the "potassium box" may identify new non-depolarizing methods of achieving arrest under single-dose conditions. The KATP-sensitive potassium (KATP) channel openers were explored for use as non-depolarizing agents for cardioplegia. The combination of adenosine and lidocaine (adenocaine) shows promise as a non-depolarizing cardioplegic agent.
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