Hazem B. Fallouh

Esmolol cardioplegia: the cellular mechanism of diastolic arrest

AIMS Esmolol, an ultra-short-acting beta-blocker, acts as a cardioplegic agent at millimolar concentrations. We investigated the mechanism by which esmolol induces diastolic ventricular arrest. METHODS AND RESULTS In unpaced Langendorff-perfused rat hearts, esmolol (0.03-3 mmol/L) had a profound negative inotropic effect resulting in diastolic arrest at 1 mmol/L and above. This inhibition of contraction was maintained during ventricular pacing. At 3 mmol/L, esmolol also abolished action potential conduction. To determine the cellular mechanism for the negative inotropism, we measured contraction (sarcomere shortening) and the calcium transient (fura-2 fluorescence ratio; Ca(tr)) in electrically-stimulated rat ventricular myocytes at 23 and 34 degrees C. The decrease in contraction (by 72% at 23 degrees C, from 0.16 +/- 0.01 to 0.04 +/- 0.01 microm, P < 0.001) was similar to that of isolated hearts and was caused by a large decrease in Ca(tr) (from 0.13 +/- 0.02 to 0.07 +/- 0.02, P < 0.001). There was no additional effect on myofilament Ca(2+) sensitivity. Esmolols effects on contraction and Ca(tr) were not shared or altered by the beta-blocker, atenolol (1 mmol/L). Sarcoplasmic reticulum inhibition with thapsigargin did not alter the inhibitory effects of esmolol. Whole-cell voltage-clamp experiments revealed that esmolol inhibited the L-type calcium current (I(Ca,L)) and the fast sodium current (I(Na)), with IC(50) values of 0.45 +/- 0.05 and 0.17 +/- 0.025 mmol/L, respectively. CONCLUSION Esmolol at millimolar concentrations causes diastolic ventricular arrest by two mechanisms: at 1 mmol/L (and below), the pronounced negative inotropic effect is due largely to inhibition of L-type Ca(2+) channels; additionally, higher concentrations prevent action potential conduction, probably due to the inhibition of fast Na(+) channels.

In patients with acute aortic intramural haematoma is open surgical repair superior to conservative management

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in patients with acute aortic intramural haematoma (IMH) is open surgical repair superior to conservative management. IMH is defined as a clinical condition related to but pathologically distinct from aortic dissection. In this potentially lethal entity, there is haemorrhage into the aortic media in the absence of an intimal tear. Altogether more than 204 papers were found using the reported search terms, from which six systematic reviews represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. IMH represents 17% of all dissections, whereas in postmortem studies this condition is found in 4-13%. The 30-day mortality of IMH is 24% (36% with type A and 12% with type B IMH; P<0.05). With surgical repair, 30-day mortality of type A IMH was 14% for patients treated surgically and 36% for patients treated medically with a P-value of 0.02. Survival at 1, 2, 3, 5 and 10 years was respectively: 81+/-21%, 87+/-8%, 83+/-6%, 65+/-22% and 44+/-14%. In contrast, with 8% mortality associated with medical treatment, prognosis of type B IMH is more favourable without surgical intervention, the latter associated with a 30-day mortality of 33% (P<0.05). Symptomatic patients and those with rapid progression or overt dissection during follow-up need emergent surgery. Ascending aortic diameter of >50 mm or subadventitial haematoma thickness of >12 mm should be considered as the candidates for early surgery. Although IMH seems to have an improved prognosis over aortic dissection, survivors of IMH are at significant risk for progressive aortic abnormalities, including aortic rupture, aneurysm, and ulceration. We conclude that surgical treatment of aortic IMH involving the ascending aorta with open distal replacement of ascending aorta results in lower mortality and longer survival compared to conservative management. IMH affecting the descending aorta can be managed with medical or endovascular interventional approach. In this latter group, serial imaging of the aorta is recommended, as aneurysm formation is not uncommon.

Is ministernotomy superior to conventional approach for aortic valve replacement

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: is ministernotomy superior to conventional approach for aortic valve replacement (AVR)? Altogether, more than 115 papers were found using the reported search, of which six represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that ministernotomy can be performed safely for AVR, without increased risk of death or other major complication; however, few objective advantages have been shown. Ministernotomy can be offered on the basis of patient choice and cosmesis rather than evident clinical benefit.

Does intermittent cross-clamp fibrillation provide equivalent myocardial protection compared to cardioplegia in patients undergoing bypass graft revascularisation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: does intermittent cross-clamp fibrillation provide equivalent myocardial protection compared to cardioplegia in patients undergoing bypass graft revascularisation? Altogether, 58 papers were found using the reported search, of which 13 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We identified 13 studies, of which eight were randomised prospective trials. None of these studies found increased mortality, seven analyzed serum cardiac enzymes and showed that intermittent ischemic arrest provides equal or better protection compared to cardioplegic techniques. Two studies found an increased usage of inotropes and intra aortic balloon pump (IABP) in the intermittent ischemic arrest group. We conclude that intermittent cross-clamp fibrillation is a versatile and cost-effective method of myocardial protection, with the immediate postoperative outcome comparable to cardioplegic arrest in first-time coronary artery bypass graft (CABG). The ischaemic duration associated with intermittent cross-clamp fibrillation is invariably shorter than that associated with cardioplegic arrest, and this may be one explanation for the comparable outcomes. There may also be an element of preconditioning protection during the intermittent cross-clamp fibrillation method, as has been shown experimentally. During elective CABG in patients with no clinical evidence of aortic or cerebro-vascular disease, the incidence of peri-operative microemboli (ME) and postoperative neuropsychological disturbances are shown to be comparable with both techniques of myocardial preservation.

Late embolization to the aortic arch of an Amplatzer Device used to occlude a baffle leak

From Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom. Disclosures: None. Received for publication March 26, 2008; revisions received June 5, 2008; accepted for publication Sept 1, 2008; available ahead of print Jan 27, 2009. Address for reprints: Prem Venugopal, MCh, FRCS, Department of cardiac Surgery, East wing, St Thomas’ Hospital, Lambeth Palace Rd, London SE1 7EQ, United Kingdom. (E-mail: vpremsundar@gmail.com. J Thorac Cardiovasc Surg 2010;139:e28-9 0022-5223/

Ischemic Preconditioning and Lung Preservation

36.00 Copyright 2010 by The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2008.09.007

New Approaches to Cardioplegia: Alternatives to Hyperkalemia

Postoperative lung complications, arising from lung injury, occur during conventional cardiac surgery and during transplantation of the lung; both these procedures involve cardiopulmonary bypass (CPB). Lung injury is associated with various pathophysiological events that occur during CPB or the long-term storage of lungs during preservation. These events include ischemiareperfusion (I/R)/hypoxia-reoxygenation, inflammation, and generation of reactive oxygen species (ROS). To counteract these adverse pathophysiological effects, there are a number of techniques currently in use to protect the lung during cardiac surgery and lung transplantation. These include the use of continuous inflation or ventilation, various protective or preservation solutions, together with the potential for exploiting the endogenous protective mechanism of preconditioning. This chapter briefly reviews the causes and mechanisms of lung injury and the techniques introduced to ameliorate this injury but focuses predominantly on the current evidence for preconditioning protection of the lung, including methods of initiating preconditioning in the lung (with emphasis on potentially clinically relevant triggers) to improve lung protection or preservation.

Cardioplegia and cardiac surgery: pharmacological arrest and cardioprotection during global ischemia and reperfusion.

The current gold standard for cardioplegic arrest during cardiac surgery is to use a hyperkalemic (elevated potassium) solution (either crystalloid or blood-based). Hyperkalemia induces arrest by shifting the resting membrane potential towards a positive value (i.e. a depolarization) and is, therefore, classified as depolarized arrest. Despite its almost universal usage, depolarized arrest has a number of disadvantages that make hyperkalemia, potentially, a less than optimal means of inducing arrest. Thus, alternative arresting methods and agents, which may be beneficial, have been explored. This chapter describes the disadvantages of depolarized arrest and highlights the alternative agents that could possibly be used in a clinical setting to induce alternative means of arrest, discussing their potential advantages and disadvantages.