Techniques of assessing hypoxia at the bench and bedside.

Tissues require an adequate supply of oxygen in order to maintain normal cell function. Low oxygen tension (hypoxia) is characteristic of a number of conditions, including cancer, atherosclerosis, rheumatoid arthritis, critical limb ischaemia, peripheral vascular disease, and ischaemic heart disease. Tissue hypoxia is found in tumours, atherosclerotic plaque, and ischaemic myocardium. There is a growing interest in methods to detect and assess hypoxia, given that hypoxia is important in the progression of these diseases. Hypoxia can be assessed at the level of the whole organ, tissue, or cell, using both invasive and non-invasive methods, and by a range of immunohistochemical, biochemical, or imaging techniques. This review describes and critiques current methods of assessing hypoxia that are used at the bench and in clinical practice.

Effects of platelet transfusion on post cardiopulmonary bypass bleeding.

A common complication of cardiopulmonary bypass (CPB) surgery is post-operative bleeding that may result in re-exploration. Bleeding is often due to the coagulopathy that follows the procedure, rather than the surgical technique. Etiology of this coagulopathy has been attributed to platelet dysfunction. We reviewed the medical records of 592 patients who had undergone CPB surgery between 1992 and 1994. Bleeding times (both pre and post operative) in treated (those who received platelets) and untreated patients were recorded where available. Both groups showed a rise in bleeding time (295 sec versus 192 sec, respectively, p<0.001). However, the treated group had a greater increase in the bleeding time compared to the un-treated (p<0.05). The result was the same when we compared 2 subgroups with similar pre-operative bleeding times. When the treated group was subdivided into those who received >10 units of platelets and those who received <10 units, there was no significant difference in the increase in their bleeding times (p>0.1). Administration of platelets did not improve bleeding time abnormalities induced by CPB. Both treated and untreated groups had a significant rise in their bleeding times, irrespective of the amount of platelets administered. The mean rise in the bleeding time in patients who bled significantly to require surgical re-exploration (but did not receive platelets) was not significantly different from those who received platelets. These observations suggest that the administration of platelets has no clinical benefit in improving bleeding time following CPB.

Incidence of postinfarction aneurysm within one month of infarct. Experiences with sixteen patients in Hawaii.

BACKGROUND: We report on sixteen patients with a left ventricular aneurysm presenting at less than a month following myocardial infarction. METHODS: All patients had significant left anterior descending coronary artery disease, and in eight cases (50%), this was the only significant pathology. Two patients who were treated conservatively, died within three months of infarction. RESULTS: Of the fourteen surgically treated patients, one died. There have been two late deaths, one at ten months and the other at four years postinfarction. Patients who present early after infarction, usually have a large anterior aneurysm, requiring early surgical repair with ventricular aneurysmectomy and revascularization. This group of patients showed a higher risk for major complications (such as thrombo-embolism, arrhythmias) and/or death. Emergency coronary artery bypass surgery may prove beneficial in the prevention of aneurysm formation by revascularizing the viable but ischemic tissue in that area.

Effects of gastrojejunostomy on pancreatic and gastric carcinoma, pancreatitis, gastric ulcer and other disease states of the gastro-intestinal tract.

BACKGROUND: To evaluate the palliative effects of gastrojejunostomy in patients who have been diagnosed with pancreatic and gastric carcinoma, and other disorders of the gastrointestinal tract. EXPERIMENTAL DESIGN: retrospective medical records review. SETTING: Honolulu area teaching hospital. PATIENTS/PARTICIPANTS: one hundred and thirty-nine patients, 27 of whom had diagnosed pancreatic carcinoma while the remainder had other diagnoses ranging from gastric carcinoma, gastric ulcer, and cancers of nearby anatomical structures such as the ampulla of Vater, between 1985 and 1990. RESULTS: Forty-eight percent (48%) of pancreatic cancer patients were female. The group consisted of 30% Japanese, 30% Caucasian, and 15% Hawaiians/part Hawaiians. Six (22%) underwent a Roux-en-Y gastrojejunostomy (GJ), thirteen (48%) obtained a loop GJ, while the remainder (30%) had a Whipple. Seven (26%) had a biliary bypass besides their GJ. No significant difference existed with regard to the failure of GJ, whether it was performed on a patient with pancreatic cancer or for any other diagnosis. Incidence of delayed gastric emptying was similar between the two groups. CONCLUSIONS: Gastrojejunostomy is effective in patients with pancreatic cancer, and meets the goal of effective gastro-intestinal function regardless of the initial diagnosis.

Effects of gastrojejunostomy on pancreatic and gastric carcinoma, pancreatitis, gastric ulcer and other disease states of the gastro-intestinal tract.

BACKGROUND: To evaluate the palliative effects of gastrojejunostomy in patients who have been diagnosed with pancreatic and gastric carcinoma, and other disorders of the gastrointestinal tract. EXPERIMENTAL DESIGN: retrospective medical records review. SETTING: Honolulu area teaching hospital. PATIENTS/PARTICIPANTS: one hundred and thirty-nine patients, 27 of whom had diagnosed pancreatic carcinoma while the remainder had other diagnoses ranging from gastric carcinoma, gastric ulcer, and cancers of nearby anatomical structures such as the ampulla of Vater, between 1985 and 1990. RESULTS: Forty-eight percent (48%) of pancreatic cancer patients were female. The group consisted of 30% Japanese, 30% Caucasian, and 15% Hawaiians/part Hawaiians. Six (22%) underwent a Roux-en-Y gastrojejunostomy (GJ), thirteen (48%) obtained a loop GJ, while the remainder (30%) had a Whipple. Seven (26%) had a biliary bypass besides their GJ. No significant difference existed with regard to the failure of GJ, whether it was performed on a patient with pancreatic cancer or for any other diagnosis. Incidence of delayed gastric emptying was similar between the two groups. CONCLUSIONS: Gastrojejunostomy is effective in patients with pancreatic cancer, and meets the goal of effective gastro-intestinal function regardless of the initial diagnosis.

Effect of anticoagulants on the incidence of late pericardial tamponade following open heart surgery. The Hawaii experience.

We report on 17 cases of late pericardial tamponade (LPT, > 60 hours postoperatively) occurring post aortic and/or mitral valve replacement or coronary artery bypass graft surgery between 1979 and 1994. This includes one patient in whom LPT occurred twice. These cases were found from a search of 374 patients including those who were diagnosed with hemorrhagic complications secondary to open heart surgery, pericardial effusion and tamponade, those who underwent pericardiocentesis and a randomly picked group of patients. The mean age of the group was 57.8 years and included 11 males and 6 females. Due to the relatively small size of our sample (reflecting the infrequency of this complication) we force matched this tamponade group to look for any relationships that may exist between the incidence of LPT and anticoagulant therapy. No significant difference was found between the two groups with documented preoperative anticoagulant therapy (number of days; p > 0.2) or in relation to coagulation tests (prothrombin time, partial thromboplastin time and platelet counts; p > 0.2). In our case series, anticoagulant therapy did not appear to significantly affect the incidence of LPT.

Measurement of oxygen free radicals in a rabbit shock lung model. Effect of superoxide dismutase and retinol.

OBJECTIVES: To develop an isolated rabbit lung model in which oxygen free radical activity could be measured and to examine the effects on the model of oxygen free radical scavengers. DESIGN: Prospective, randomized study. SETTING: A clinical and basic research facility attached to a teaching hospital. PARTICIPANTS: Twenty-five New Zealand white rabbits weighing 3.5 to 4.5 kg. INTERVENTIONS: The mechanism of lung injury by oleic acid or by phorbol myristate acetate (20 ng/mL) plus polymorphonuclear neutrophils (PMA-PMN) in an ex vivo rabbit shock lung model may be the production of oxygen free radicals. Using a standard heart-lung preparation from these rabbits, baseline mean pulmonary artery pressure was maintained at 15 mm Hg and the mean airway pressure at 10 mm Hg. Experimental perfusates were infused over 30 minutes, followed by Krebs-Henseleit solution, pH 7.4. Dimethyl pyrroline oxide trapped oxygen free radicals, levels of which were measured by electron paramagnetic resonance spectroscopy. Lung injury was assessed by light and scanning electron microscopy and by lung weight. RESULTS: A 5-fold increase in pulmonary artery pressure (P < .001) and a nearly 3-fold increase in mean airway pressure (P < .001) were observed in both the oleic acid and PMA-PMN models. Superoxide dismutase (20,000 U/kg), but not retinol palmitate (2000 U), prevented lung injury, the increases in pulmonary artery pressure and mean airway pressure, and the increase in oxygen free radicals in the PMA-PMN model. There were no increases in oxygen free radicals in the control, oleic acid, or PMA-PMN/superoxide dismutase groups (n = 5 in each group). Maximum mean +/- SD increases in oxygen free radicals were 112 +/- 22 nmol/L in the PMA-PMN group (P < .003, n = 5) and 108 +/- nmol/L in the PMA-PMN/retinol group (P < .003, n = 5). CONCLUSIONS: The mechanism of lung injury in the PMA-PMN model is an increase in oxygen free radicals, because superoxide dismutase prevents both the rise in oxygen free radicals and lung injury. Administration of retinol does not prevent lung injury. Oleic acid produces injury not by an increase in oxygen free radicals but rather by another, unknown mechanism.

Detection of mutagen specific adduct formation in DNA using sequencing methodology.

It has been reported that single stranded viral DNA reacts with the carcinogen, chloroacetaldehyde at specific hot spots (Premaratne et al., 1993 Int. J. Biochem. 25, 1669-1672). We tested this occurrence with several other mutagens and potential carcinogens. A series of chemicals (chloroacetaldehyde, methyl, ethyl, and propyl nitro nitrosoguanidine, hydrazine, 2,4 dinitrophenyl hydrazine, hydroxylamine and methyl methanesulfonate) were each separately reacted with viral M13mp18 DNA for 2 hr at 37 degrees C and pH 4.9. The locations of adduction were identified as points of chain termination (or polymerase fall off) when the reacted DNA was subjected to a modified sequencing procedure that had ample regular labeled and unlabeled nucleotides but lacked dideoxy chain termination mixtures. Chain termination was observed to occur at specific, non-random, sites rather than with equal probability at all bases of the DNA. Chemicals with similar structures had identical points of "fall off". The pattern of chain termination appears to be unique to each class of compounds and is independent of temperature, pH, and salt concentration. Termination is believed to occur when the DNA polymerase encounters an adduct. Mutagens of different unrelated structures when reacted with this DNA produced different sites of adduct formation, while the alkyl nitro nitrosoguanidines, compounds with homologous structure showed identical points of chain termination.

Atrial myxomas: experiences with 35 patients in Hawaii.

BACKGROUND: Thirty-five patients with an intracardiac myxoma underwent excision of the tumor in Hawaii between 1974 and 1993. PATIENTS AND METHODS: There were 28 female and 7 male patients in the group. Their ages ranged from 11 to 79 years (mean 48) with the majority (71%) between 30 and 60 years old. The patients' medical records were reviewed and special attention was paid to clinical presentation, methods of diagnosis, operative findings, and postoperative course. RESULTS: No ethnic predisposition was found. Forty-six percent of the presenting symptoms were cardiac (congestive heart failure 26%, palpitations 14%, and syncope 6%) while arterial embolization accounted for 11%. Diagnosis was made by angiography, echocardiography, or gated cardiac blood pool imaging. All were reliable, but two-dimensional (2-D) echocardiography was used most often, with no false-positive or false-negative results. There were 32 left atrial, 2 right atrial, and 1 biatrial myxomas. Limited septectomy was performed in most cases, but 9 patients (26%) required Dacron patch repair of the atrial septum. There was 1 death from a cerebrovascular accident the day after the removal of a left-sided atrial myxoma. Other patients had few minor postoperative complications. One patient presented with a recurrence 8 years after resection at another institution; no further recurrences were found. CONCLUSIONS: We conclude that due to the non-specific presentation of atrial myxoma, a high index of suspicion is needed. The diagnostic method of choice is 2-D echocardiography. Limited septectomy is a safe procedure, but close follow-up for at least 10 years may be needed to rule out recurrence.

Effects of perfluorocarbon exchange transfusion on reducing myocardial infarct size in a primate model of ischemia-reperfusion injury: a prospective, randomized study.

BACKGROUND: This study was undertaken to test the hypothesis that perfluorocarbons were able to reduce myocardial infarct size in a baboon model of ischemia-reperfusion injury. Exchange transfusion of perfluorocarbons has been shown to reduce myocardial infarct size in the dog, who, unlike the baboon, has an extensive collateral circulation. METHODS: After 15 minutes of occlusion of the left anterior descending coronary artery, 14 baboons were bled to attain a hematocrit of 24% to 26% and were simultaneously transfused, six with Fluosol-DA 20% emulsion and eight with FC-43 emulsion. After 2 hours of ligation, the coronary arteries were reperfused. Baboons were killed 24 hours after ligation, and the hearts were excised. Microvascular dye was infused into the coronary artery to delineate its perfusion bed. Ratios of the mean volume of infarct to the mean volume of perfusion bed were calculated and compared by use of planimetry. A similar protocol was followed in two other groups of baboons except that lactated Ringer's solution was infused into six of them, whereas eight had no exchange transfusions. RESULTS: The ratios of the mean volume of infarct to the mean volume of perfusion bed of the four groups were as follows: Fluosol-DA, 38.1% +/- 7.5%; FC-43, 37.7% +/- 8.3%; lactated Ringer's, 46.9% +/- 10.5%; controls, 65.6% +/- 6.9%. Statistical significance was reached when comparing both perfluorocarbon-treated groups with the controls (p < 0.05 for both groups) but not significant when comparing them with the Ringer's lactate-treated group. CONCLUSIONS: Results suggest that the beneficial effects of exchange transfusion with the perfluorocarbons may be primarily due to hemodilution.