Is there a role for surgery in the management of giant B-cell right atrial lymphoma?

We describe a case of a giant right atrial large B-cell lymphoma treated with initial surgical excision followed by postoperative chemotherapy. The patient had no clinical evidence of recurrence through 87 months after her hospital discharge. To our knowledge, this is the first reported case of long-term survival following this method of disease management. The discussion reviews the current status of chemotherapy for cardiac lymphomas and the pros and cons of treatment option algorithms.

Does warm blood retrograde cardioplegia preserve right ventricular function?

BACKGROUND: Efficacy of warm blood retrograde cardioplegia in preserving right heart function remains controversial. The current study was conducted to gauge the preservation of right ventricular function after warm blood retrograde cardioplegia. METHODS: We studied 75 consecutive patients undergoing isolated heart valve procedures with warm blood retrograde cardioplegia as the exclusive mode of preservation. Right ventricular radionuclide ejection fraction and hemodynamic measurements using a pulmonary artery catheter were calculated before and within 3 days after operation. RESULTS: Postoperative radionuclide right ventricular ejection fraction was well preserved at 0.4686 +/- 0.0122 compared with 0.4327 +/- 0.0255 preoperatively (p = 0.7064). Right ventricular systolic work index improved from 5.82 +/- 0.52 to 8.97 +/- 0.60 g x m/m2 (p < 0.0001) and cardiac index increased from 2.40 +/- 0.09 to 2.92 +/- 0.11 L/m2 (p < 0.0001). When right ventricular systolic work index was correlated with preload, 30 patients moved up and down on the same ventricular function curve and 42 moved to a higher inotropic curve postoperatively. Only 3 patients demonstrated decreased inotropy. CONCLUSIONS: In the clinical setting warm blood retrograde cardioplegia used as the exclusive mode of myocardial preservation provides adequate protection of the right heart.

Does cardioplegia type affect outcome and survival in patients with advanced left ventricular dysfunction? Results from the CABG Patch Trial.

BACKGROUND: There is controversy regarding which cardioplegic solution, temperature, and route of administration provides superior protection. The CABG Patch Trial enrolled a high-risk group of coronary artery disease patients with an ejection fraction of <36%. Thus, they constitute an ideal group to benefit most from optimal cardioplegic protection. METHODS AND RESULTS: All patients randomized into the trial were compared with respect to the use of blood and crystalloid cardioplegia. In addition, a questionnaire was sent to surgeons requesting blood cardioplegic temperature and route. Patients receiving crystalloid cardioplegia versus those receiving blood cardioplegia were found to have significantly more operative deaths (2% versus 0.3%, P:=0.02), postoperative myocardial infarctions (10% versus 2%, P:<0.001), shock (13% versus 7%, P:=0. 013), and postoperative conduction defects (21.6% versus 12.4%, P:=0. 001). Despite this, early death (6% crystalloid versus 4% blood cardioplegia) and late death (24% crystalloid versus 21% blood cardioplegia) statistics were not significantly different. Patients receiving normothermic blood had less postoperative right ventricular dysfunction (10%) than did patients receiving cold blood (25%) or cold blood with warm reperfusion (30%) (P:=0.004). There was no significant difference in early or late death. Finally, patients who received combined antegrade and retrograde cardioplegia had significantly less inotrope use (71% versus 84%, P:=0.002), right ventricular dysfunction (23% versus 41%, P:=0.001), and postoperative balloon pump use (12% versus 19%, P:=0.02) than did those who received antegrade cardioplegia. There was no difference in survival. CONCLUSIONS: Blood cardioplegia and combined antegrade and retrograde cardioplegia are superior to crystalloid and antegrade cardioplegia alone for postoperative morbidity. Despite this, there is no significant difference in early or late survival.

Myocardial protection by preconditioning of heart with losartan, an angiotensin II type 1-receptor blocker: implication of bradykinin-dependent and bradykinin-independent mechanisms.

BACKGROUND: Ischemic preconditioning (PC) represents a state-of-the-art technique for myocardial preservation. Although certain intracellular mediators have been shown to play a role in PC, the exact nature of the trigger for PC is not known. Our previous study demonstrated that intracellular bradykinin released from the heart during ischemia/reperfusion plays a role in myocardial preservation. This study was undertaken to further examine the mechanism of bradykinin-mediated PC. METHODS AND RESULTS: Since the bradykinin B(2) receptor is likely to provide cardioprotection by blocking angiotensin II formation, we determined the effects of an angiotensin II type 1 (AT(1)) receptor blocker, losartan, and a bradykinin B(2) receptor blocker, HOE 140, on myocardial protection. Isolated rat hearts were perfused initially by the Langendorff mode with Krebs-Henseleit buffer (KHB) for 15 minutes in the absence (control) or presence of losartan (4.5 micromol/L) and/or HOE 140 (10 micromol/L). After conversion to the working mode for 10 minutes (baseline), randomly assigned control and experimental hearts were subjected to 30 minutes of normothermic global ischemia followed by 2 hours of reperfusion. Myocardial function, infarct size, cardiomyocyte apoptosis, and amount of bradykinin/angiotensin released from the hearts were measured at baseline and during reperfusion while in the working mode. Significant postischemic ventricular recovery was demonstrated by improved developed pressure and aortic flow and reduced myocardial infarct size and apoptotic cell death with losartan, whereas the reverse was true for HOE 140. The functional recovery and infarct size-lowering ability of losartan were partially blocked and the antiapoptotic function of losartan was completely blocked by HOE 140. CONCLUSIONS: The results document that losartan reduced whereas HOE 140 increased myocardial ischemia/reperfusion injury by blocking AT(1) and bradykinin B(2) receptors, respectively, suggesting a role of the bradykinin B(2) receptor in PC. Losartan provided cardioprotection through both bradykinin-dependent and bradykinin-independent mechanisms.

Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation.

BACKGROUND: Ischemic preconditioning has been proven to be a powerful tool for myocardial protection in the setting of ischemia and reperfusion. A new drug to provide pharmacologic preconditioning, monophosphoryl lipid A (MLA), was administered 24 hours before an acute coronary occlusion in pigs to determine the effect on pharmacologic preconditioning. METHODS: Two studies were completed. In the first, swine were distributed into five groups: group I, control; group II,. aminoguanidine (AMG) (30 mg/kg), a selective inducible nitric oxide synthase (iNOS) blocker; group III, MLA (10 microg/kg); group IV, MLA (35 microg/kg); and group V, MLA and AMG (35 microg/kg and 30 mg/kg, respectively). Twenty-four hours after administration of the MLA, AMG, or both, regional left anterior descending coronary artery ischemia was induced for 15 minutes followed by one hour of global normothermic cardioplegic arrest and three hour reperfusion. Left ventricular function, tissue injury, and percentage of myocardial infarction were measured. Left ventricular myocardium in the left anterior descending coronary artery region was sampled for iNOS messenger RNA (mRNA) during ischemia and reperfusion. In the second study, pigs were sacrificed 0, 4, 6, 8, and 24 hrs after MLA/AMG administration for iNOS mRNA determination in nonischemic myocardium. RESULTS: Use of MLA significantly improved postischemic ventricular function, and reduced creatinine kinase release and percentage of infarction. Monophosphoryl lipid A induced expression of iNOS mRNA in nonischemic myocardium within four hours of administration which returned to base line by 24 hours. Normothermic regional ischemia then induced expression of iNOS mRNA, which returned to base line during reperfusion. Aminoguanidine completely abolished both MLA-induced and ischemia-induced iNOS mRNA and blocked the beneficial effects of MLA. CONCLUSIONS: Use of MLA can provide myocardial preservation through enhanced expression of iNOS mRNA.

Risk of dysphagia after transesophageal echocardiography during cardiac operations.

BACKGROUND: Dysphagia can be a significant complication following cardiac operations. This study evaluates its incidence and relationship to intraoperative transesophageal echocardiography (TEE) for specific indications versus known factors such as stroke or prolonged intubation. METHODS: Records of 838 consecutive cardiac surgical patients were reviewed, and categorized into those who received TEE for specific indications versus those who did not (nonTEE). Dysphagia was recorded when symptoms were confirmed by barium cineradiography. Multiple logistic regression identified significant factors causing dysphagia. RESULTS: TEE was significantly related to the development of postoperative dysphagia by multiple logistic regression (p < 0.001). After controlling for other significant factors (stroke, left ventricular ejection fraction, intubation time, duration of operation), the odds of dysphagia for TEE patients was 7.8 times greater than for nonTEE patients. CONCLUSIONS: TEE may be an independent risk factor for dysphagia following cardiac operations.

Is there a relationship between systemic perfusion temperature during coronary artery bypass grafting and extent of intraoperative ischemic central nervous system injury?

OBJECTIVE: This study was designed to compare the volume of cerebral infarction in patients operated on under either hypothermic or tepid/normothermic perfusion for coronary revascularization. METHODS: A randomized trial with preoperative, postoperative, and late neurologic evaluation was conducted in patients undergoing coronary revascularization having either hypothermic or tepid/normothermic perfusion for coronary revascularization. The goal was to determine whether perfusion temperature correlated with neurologic dysfunction associated with coronary artery bypass. RESULTS: Twelve intraoperative ischemic strokes occurred during coronary revascularization in a series of 291 patients. Six of these were in the group receiving hypothermic perfusion and 6 in groups receiving the tepid/normothermic perfusion. Measuring the infarct volume documented that 3 of the strokes in each group resulted in minor or small infarcts and 3 in each group were significant, major strokes. The volume of infarction, whether including all 6 patients in each group or only those with major strokes, was no different between the hypothermic and the tepid/normothermic groups. CONCLUSIONS: In this series of 291 patients randomized to perfusion temperature, we observed no relationship between the size of a cerebral ischemic infarct and the perfusate temperature during coronary revascularization.

Molecular targets of gene therapy.

Ischemic reperfused heart represents a potential target for gene therapy because gene transfer can represent an alternate pharmacological approach to protect the heart from cellular injury. Gene therapy may be particularly useful to deal with previously unapproachable problems. For myocardial preservation, gene therapy could replace those pharmacological interventions when drugs are delivered locally by sustained release with the help of mechanical device, eg, implants. In this review, attempts are made to define the molecular targets for gene therapy primarily applicable to myocardial preservation associated with ischemia and reperfusion. It has been emphasized that for successful gene transfer, not only characterization of proper targets and elimination of undesirable side effects are necessary, but also the therapy must be proven superior compared to other pharmacological interventions including surgery.

Ischemic preconditioning reduces apoptosis by upregulating anti-death gene Bcl-2.

BACKGROUND: Reperfusion of ischemic myocardium causes cardiomyocyte apoptosis in concert with downregulation of Bcl-2 gene. Ischemic preconditioning (PC) mediated by cyclic episodes of short-term ischemia and reperfusion reduces apoptotic cell death. PC also triggers a signaling pathway by potentiating tyrosine kinase phosphorylation leading to the activation of p38 MAP kinase and MAPKAP kinase 2. The nuclear transcription factor, NFkappaB, plays a crucial role in this signaling process. Because NFkappaB is a target of oxygen free radicals and Bcl-2 is an antioxidant gene, we hypothesized that reactive oxygen species might play a role in the signaling process. METHODS AND RESULTS: Isolated rat hearts were perfused in the absence or presence of either dimethyl thiourea (DMTU), a hydroxyl radical scavenger, or SN50 peptide, a NFkappaB blocker. Hearts were then subjected to PC by 4 repeated episodes of 5-minute ischemia, each followed by 10 minutes reperfusion. All hearts were then made globally ischemic at normothermia for 30 minutes followed by 2 hours of normothermic reperfusion. Creatine kinase release and malonaldehyde formation were determined in the coronary effluent collected during reperfusion. At the end of each experiment, hearts were processed for infarct size determination and analyses of apoptosis, DNA fragmentation, NFkappaB, and Bcl-2. Myocardial infarction was reduced by PC. DMTU and SN50 abolished this cardioprotective effect of PC. PC resulted upregulation of Bcl-2 gene which was partially prevented by DMTU and SN50. Both ischemia/reperfusion and PC caused nuclear translocation and activation of NFkappaB, which was blocked by both DMTU and SN50. PC reduced cardiomyocyte apoptosis which was partially inhibited by DMTU and SN50. A substantial number of apoptotic cardiomyocytes were identified in the hearts subjected to 30 minutes ischemia and 2-hour reperfusion. PC significantly inhibited the extent of cardiomyocyte apoptosis and DMTU and SN50 reversed it only minimally. CONCLUSIONS: The results demonstrate that reactive oxygen species play a crucial role in signal transduction mediated by PC. This signaling process appears to involve NFkappaB. NFkappaB becomes translocated and activated by both ischemia/reperfusion, which induces apoptosis and PC which reduces apoptosis. However, the amount of NFkappaB binding activity is significantly higher in the PC hearts compared with ischemic reperfused hearts. The upregulation of the antioxidant gene, Bcl-2, is inversely correlated with the reduction of cardiomyocyte apoptosis associated with PC.

Influence of cardiopulmonary bypass perfusion temperature on neurologic and hematologic function after coronary artery bypass grafting.

BACKGROUND AND METHODS: A National Institutes of Health-sponsored trial (1994 to 1998) randomized patients undergoing coronary artery bypass grafting that required three or more grafts to receive perfusion at either cold (20 degrees C), tepid (32 degrees C), or warm (37 degrees C) temperature. The goal of the study was to evaluate morbidity, primarily neurologic dysfunction and secondarily hematologic factors. One thousand seven hundred seventy-seven patients were screened and 291 enrolled. Neurologic function was studied by a dedicated pool of blinded neurologists. A standard test battery termed the Mathew Scale using three subscales--cognitive function, elemental skills, and disability--was used to study central nervous system function. Hematologic function was assessed in 53 of the 291 patients with measurements of postoperative fibrinolytic potential. RESULTS: All preoperative and operative data were comparable between groups. A decrease in Mathew Scale was seen in 69% of patient from before operation to immediately after operation. However, between the early postoperative study and the 1-month follow-up, 48% of patients had returned to baseline. There was no difference noted across temperature groups in any neurologic parameter of function. In all, 55% of the group were at or above their preoperative level at 1 month. Forty-nine patients suspect for cerebrovascular accident had a computed tomographic scan, but only 13 (4.5%) had a documented cerebrovascular accident (4 patients in the warm, 3 in the tepid, and 6 patients in the cold group). Fibrinolytic changes correlated with perfusion temperature documented that fibrinolysis was most active at 37 degrees C. Thus, increasing perfusate temperature increases fibrinolysis, which was associated with reoperation for bleeding in 4% warm group patients, 1% tepid, and 0% cold group patients (0.1 > p > 0.05). No other perioperative complications were temperature related. There were 4 deaths (1.4%) (1 in the warm group, 2 in the tepid group, and 1 in the cold group). CONCLUSIONS: (1) Persistent postoperative neurologic dysfunction at 1 month occurs in 36% of patients undergoing coronary artery bypass grafting and is not related to a cerebrovascular accident; 2) perfusion temperature has no relationship to neurologic function after bypass; and 3) fibrinolytic activity is greatest at warm temperatures.

Fenestrated felt facilitates anastomotic stability and safety in "off-pump" coronary bypass.

Metal stabilizing devices used in beating heart surgery, although largely effective, occasionally slip or cause lacerations of epicardial veins or myocardium, resulting in blood loss that requires time-consuming corrective maneuvers. The use of a fenestrated felt as a cushion in conjunction with the stabilizers eliminates slipping and/or trauma, thus facilitating coronary anastomoses on the beating heart.

The 'primeless pump': a novel technique for intraoperative blood conservation.

PURPOSE: Hemodilution during cardiopulmonary bypass may lead to anemia requiring intraoperative transfusions. Prime removal from the cardiopulmonary bypass circuit was used to limit dilution and intraoperative transfusions. METHODS: The technique of prime removal consists of arterial and then venous side evacuation of crystalloid prior to cardiopulmonary bypass. The effectiveness of this technique, to maintain a higher hematocrit and reduce intraoperative transfusions, was studied prospectively in two consecutive groups of patients undergoing coronary revascularization (controls versus primeless). RESULTS: Intraoperative hematocrits were significantly higher (P < 0.0001) and transfusions lower (4%) in the primeless versus the control group (19%) (P = 0.003). Prime removal is of particular benefit in anemic (hematocrit < or = 35%) and/or small patients (body surface area < or = 2 m2). CONCLUSION: The technique of prime removal is simple, safe and cost-effective, reducing intraoperative transfusions, especially in small and/or anemic patients. It could be part of blood conservation strategies in most adult cardiac operations.

Use of extrafascially harvested radial artery for coronary artery revascularization: technical considerations.

BACKGROUND: The use of the radial artery for coronary artery revascularization was abandoned due to its tendency for spasm; the revival was attributed to improved harvesting technique as well as the use of calcium channel blockers. METHODS: Between February 1996 and June 1997, the radial artery graft was used in 77 of 89 consecutive patients undergoing coronary artery bypass graft surgery. Only the patients with positive Allen's test or forearm deformity were denied the use of the radial artery. We used an extrafascial, no-touch technique using low-strength electrocautery for harvesting the radial artery. Calcium channel blockers were not used in any of these patients. RESULTS: There were no early deaths. No patient sustained perioperative myocardial infarction or required intra-aortic balloon pump. Only one patient required inotropic agents. Three noncardiac late deaths occurred during the follow-up of 6 to 24 months. No early or late ischemic or functional forearm disability was reported in any of the patients. CONCLUSIONS: The radial artery is easy to harvest and safe to use routinely. When harvested extrafascially, diltiazem infusion may not be necessary. Maximal arterial-global revascularization using the left internal thoracic artery-to-left anterior descending coronary artery and radial artery-to-circumflex artery system may improve the early and long-term results.

Reoperative median sternotomy using a cast spreader.

Repeat median sternotomy carries a high mortality rate secondary to a higher incidence of injury to the underlying vital structures. The reported incidence of reentry accidents may be as high as 6% to 10%. We describe a new technique of redo sternotomy using a nitrogen-powered oscillating saw and a cast spreader. The new technique was used for 89 consecutive cases without any incidence of injury to the underlying structures. The use of a case spreader during repeat median sternotomy may enhance the safety of reentry.

Ischemic preconditioning attenuates apoptotic cell death associated with ischemia/reperfusion.

Apoptosis or programmed cell death is a genetically controlled response for cells to commit suicide and is associated with DNA fragmentation or laddering. The common inducers of apoptosis include oxygen free radicals/oxidative stress and Ca2+ which are also implicated in the pathogenesis of myocardial ischemic reperfusion injury. To examine whether ischemic reperfusion injury is mediated by apoptotic cell death, isolated perfused rat hearts were subjected to 15, 30 or 60 min of ischemia as well as 15 min of ischemia followed by 30, 60, 90 or 120 min of reperfusion. At the end of each experiment, the heart was processed for the evaluation of apoptosis and DNA laddering. Apoptosis was studied by visualizing the apoptotic cardiomyocytes by direct fluorescence detection of digoxigenin-labeled genomic DNA using APOPTAG in situ apoptosis detection kit. DNA laddering was evaluated by subjecting the DNA obtained from the hearts to 1.8% agarose gel electrophoresis and photographed under UV illumination. The results of our study revealed apoptotic cells only in the 90 and 120 min reperfused hearts as demonstrated by the intense fluorescence of the immunostained digoxigenin-labeled genomic DNA when observed under fluorescence microscopy. None of the ischemic hearts showed any evidence of apoptosis. These results were corroborated with the findings of DNA fragmentation which showed increased ladders of DNA bands in the same reperfused hearts representing integer multiples of the internucleosomal DNA length (about 180 bp). The presence of apoptotic cells and DNA fragmentation in the myocardium were completely abolished by subjecting the myocardium to repeated short-term ischemia and reperfusion which also reduced the ischemic reperfusion injury as evidenced by better recovery of left ventricular performance in the preconditioned myocardium. The results of this study indicate that reperfusion of ischemic heart, but not ischemia, induces apoptotic cell death and DNA fragmentation which can be inhibited by myocardial adaptation to ischemia.

Influence of the preoperative signal-averaged electrocardiogram on left ventricular function after coronary artery bypass graft surgery in patients with left ventricular dysfunction. The CABG Patch Trial.

Patients with ischemic left ventricular (LV) dysfunction often have an improved survival and life quality after coronary artery bypass grafting (CABG), in part due to an improvement in LV function. A lack of LV ejection fraction (EF) improvement postoperatively portends a worse prognosis. Recently, an abnormal preoperative signal-averaged electrocardiogram (SAECG) in patients with a severely depressed LV ejection fraction undergoing elective CABG was shown to be associated with a higher early and late postoperative mortality. The present study evaluated patients with severe LV dysfunction to identify any relation between an abnormal preoperative SAECG and postoperative changes in LV function after successful CABG. Forty-five patients with LV dysfunction (LVEF <0.36) scheduled for elective CABG underwent preoperative SAECG and both pre- and postoperative LVEF determinations using radionuclide scans. Thirty-one patients in the group had an abnormal preoperative SAECG and 14 patients had a normal preoperative SAECG. Baseline patient characteristics were similar in both groups and the mean preoperative LVEF was 0.26. Overall, LVEF improved 31% postoperatively with a significantly greater benefit noted in the group with a normal baseline SAECG (14.9+/-5.7-point vs 4.8+/-8.5-point increase, p <0.001). All patients whose LVEF did not improve or worsened postoperatively had an abnormal preoperative SAECG. No SAECG measure was altered significantly by the operation. A preoperative SAECG provides information on the postoperative functional recovery of ischemic myocardium.

A cost-effective retractor and heart stabilizer for minimal-access coronary bypass.

Exposure for internal mammary artery harvesting and immobilization of the coronary artery during the performance of minimally invasive direct coronary artery bypass grafting requires the use of appropriate retractors and instruments. We have successfully used existing retractors and instruments, modified for such use, which are reusable and cost effective. The use of such a retractor and cardiac stabilizer is described.