A vibrating probe thermal biochemical sensor.

Rapid vibration of small enzyme-thermopile biochemical sensors in solution has been observed to substantially improve their thermal noise rejection. Millimeter-order 20 Hz vibratory excursions of a thermal biosensor by a piezoelectric bender element were found to be effective in eliminating the need for temperature controlled dewars, flow streams, or special thermal environments ordinarily required to operate these sensors. Vibrated thermopiles have been made into biochemical sensors by attaching thin membrane hollow fibers to the thermopile sensing region and perfusing the lumen of the fiber with small quantities of an enzyme solution. This process can give the biosensor an extended lifetime by allowing easy replacement of the enzyme. Vibrated enzyme-thermopile biochemical sensors can be realized in a convenient and compact probe-type configuration that is directly immersible into a test solution.

In vivo and in vitro deactivation rates of PTFE-coupled glucose oxidase.

The deactivation of immobilized enzymes is a major lifetime limiting factor in several types of potentially implantable biosensors. The deactivation rate of covalently immobilized glucose oxidase was examined in vitro in mock physiologic environments and in the peritoneal cavity of mice. A first order deactivation model describes the observed exponential decay of the enzyme. Deactivation rate constants ranging from 0.198 to 1.3 per day were measured depending on experimental conditions. Enzymes immobilized on PTFE (Teflon) substrates in the peritoneal cavity of mice exhibited greater catalytic lifetimes than control samples kept in glucose solution in vitro.

Performance of a hydrogel composite pericardial substitute after long-term implant studies.

A novel composite patch has been tested as a pericardial substitute to reduce adhesion formation after cardiac surgery. The patch consists of poly 2-hydroxyethyl methacrylate (pHEMA) hydrogel reinforced with a polyethylene terephthalate (PET) mesh. The hydrogel-PET composite pericardial patches were implanted in canines for 6, 9, and 12 months. Upon termination, adhesion formation and epicardial reaction to the implant were rated. No adhesions formed between the patch and the native pericardium or epicardium. A thin fibrous layer on the epicardium progressively developed where the patch contacted the heart. The coronary anatomy remained visible. Histologically, the response to the implant was fibrous in nature. No significant signs of cellular inflammation were found. The gross appearance of the retrieved patches was nearly identical to that of preimplant patches. Mechanical tests showed no significant changes (alpha = 0.05) in patch strength or stiffness. Hydrogel water content initially increased during implantation. The thickness of the patch did not change significantly (alpha = 0.05) throughout the study. Scanning electron microscopy (SEM) revealed unequal layers of hydrogel on either side of the PET mesh and cracks in the hydrogel surfaces of retrieved patches. Both SEM and light microscopic observation of the patches showed traces of calcification in patches in the 9 and 12 month studies.

In vivo results of hydrogel composite pericardial substitutes.

In this study, two improved pericardial patches were developed and evaluated for their efficacy as pericardial substitutes. The patches are composites consisting of a hydrogel (PHEMA) that coats an underlying mesh (either ETFE or PET). Studies were conducted using subcutaneous implants in rats and pericardial patch implants in greyhound dogs. Adhesions between the substitute and pericardium and the epicardium were minimal. The ETFE composite patch caused an unacceptable epicardial reaction. The PET patch results were encouraging; the epicardium was largely unaffected by the patch.

A hydrogel pericardial patch.

Patients undergoing repeat cardiac operations are higher operative risks than those undergoing an initial cardiac procedure because adhesion formation can occur if the native pericardium is not closed. A unique composite patch that may be used to augment the pericardial tissue when primary closure is not possible has been developed. The patch is made of a hydrogel, poly (2-hydroxyethyl methacrylate), reinforced with an ethylene tetrafluoroethylene (ETFE) mesh. The mesh provides the needed mechanical properties, whereas the patch's surface properties are comparable to the hydrogel. Two types of patches were fabricated: one with the mesh weave at a perpendicular orientation and one at 45 degrees to the principle loading direction. The patches were mechanically tested and compared with canine pericardium. Ultimate tensile strength of the patches is not significantly different from canine pericardium (p less than 0.05), are the patch suture strength is nearly twice that of canine pericardium. The perpendicular patch is stiffer than canine pericardium, whereas the 45 degree patch is not (p less than 0.05). The 45 degree patch shows considerable promise as a pericardial substitute because it closely matches the properties native canine pericardium.

Thermoelectric enzyme sensor for measuring blood glucose.

A new calorimetric sensor has been developed which employs a thin-film thermopile in association with an immobilized enzyme. The thermopile detects the minute temperature rise that occurs when a specific chemical substrate is catalyzed by the enzyme. A prototype sensor is described which generates an equivalent proportional voltage response to glucose concentrations present in either buffer solution or blood. These sensors have remained useful for up to 18 days when operated intermittently for measuring glucose in buffer solutions, or for up to 4 days when operated continuously. When implanted inside cardiovascular shunts on anesthetized dogs, the sensors responded appropriately to changes in the blood glucose concentration.

Total pericardial replacement. Design and preliminary evaluation in greyhounds.

Existing pericardial substitutes, used for the prevention of pericardial and pleural adhesions to the epicardium, are in the form of a patch. To improve on this concept, an elastic, anatomically correct, implantable sac has been developed for total pericardial replacement. Total pericardial substitutes fabricated from Silastic silicone rubber and Mitrathane polyetherurethane urea were implanted in greyhound dogs and harvested at 8 weeks. Pericardial adhesions were prevented by the substitutes that remained intact. Fibrous tissue formation had occurred on the epicardium underlying the substitutes, the extent being more severe in response to the Silastic compared with the Mitrathane. However, the Silastic was superior to the Mitrathane in retention of its tensile strength and elastic modulus over the implant period (p less than 0.05). Further development of total pericardial substitutes from different materials shows promise.

Perioperative right heart failure: etiology and pathophysiology.

A considerable amount of literature has been devoted to compromise of the right ventricle in spontaneous myocardial infarction. Little information is available regarding disproportionate dysfunction of the right ventricle associated with cardiac operation and the recovery period therefrom. Recognition of the problem is of paramount importance, if support measures are to be implemented. A great deal has yet to be learned regarding the appropriate support for the acutely failing right ventricle. Much remains to be accomplished regarding the assessment of right ventricle reserve, defining the role of risk factors, and quantitating the value of measures to optimally protect the right ventricle from injury during the perioperative period. Recognizing that the integrity of the right ventricle can be altered by numerous preoperative, perioperative and postoperative factors will provide an enlightened disposition on the part of the surgical team. Awareness of these considerations in the planning and conduct of surgical procedures should reduce morbidity and mortality from perioperative right ventricular failure. The imposition of new or unexpected morbidity during operation on a relatively unrelated problem represents surgical imperfection. Appropriate effort toward minimizing insult of the right ventricle could result in significantly decreasing the incidence and severity of perioperative right ventricular failure before the impetus of the continuing clinical problem dictates improvement in techniques to more appropriately treat this frequently preventable problem.

Acute right ventricular failure is caused by inadequate right ventricular hypothermia.

The hypothesis of this study was that inadequate right ventricular hypothermia contributes to the right ventricular dysfunction occasionally observed after cardiac operations. Dogs were placed on cardiopulmonary bypass, and 60 minute periods of hypothermic myocardial ischemia were imposed. Left ventricular temperature was always maintained at 15 degrees C and right ventricular temperatures were maintained at 15 degrees C (Group I, n = 8), 25 degrees C (Group II, n = 8), and 35 degrees C (Group III, n = 8). These temperatures were produced by infusion of hypothermic crystalloid cardioplegic solution and appropriate topical cooling and heating of the left and right ventricles, respectively. Multiple indices of ventricular function were obtained 15, 30, 45, and 60 minutes after bypass and compared to prebypass control values. In all Group I animals (left ventricular temperature = 15 degrees C, right ventricular temperature = 15 degrees C), postischemic indices of right ventricular function were not different from control values (p = NS). In Group II (left ventricular temperature = 15 degrees C, right ventricular temperature = 25 degrees C), two animals died 30 and 45 minutes after bypass, respectively, of right ventricular failure. In the other six animals in Group II, all indices of right ventricular function were significantly reduced (p less than 0.05) except for right ventricular systolic pressure. In Group III (left ventricular temperature = 15 degrees C, right ventricular temperature = 35 degrees C), two animals could not be weaned from cardiopulmonary bypass because of right ventricular akinesia. Six animals were weaned from bypass, but two died 15 minutes, one died 30 minutes, and one 45 minutes after bypass. Two animals lived 60 minutes, but all indices of right ventricular function were decreased. Failure to maintain right ventricular temperatures below 25 degrees C during 1 hour of cardiac ischemia in the dog can result in fatal right ventricular failure.

Effect of intermittent infusions of glucose-containing crystalloid cardioplegic solution on myocardial tissue lactic acid and recovery of contractility.

The objective of this study was to determine the effects of single or intermittent infusions of cardioplegic solution with glucose (5 gm/L) or without glucose on myocardial tissue lactic acid and recovery of myocardial contractility following 80 minutes of total ischemia at 28 degrees C in the isolated, blood-perfused, beating rabbit heart. Ischemia without cardioplegia increased tissue lactic acid (6.79 mg/gm tissue) above the control value (0.9 mg/gm tissue), p less than 0.0025). Lactic acid following single infusions with (4.19 mg/gm tissue) or without glucose (3.67 mg/gm tissue) was significantly greater (p less than 0.0025) than tissue lactic acid following intermittent infusions with (1.06 mg/gm tissue) or without glucose (1.05 mg/gm tissue). Cardioplegic arrest in all cases significantly decreased tissue lactate accumulation when compared to arrest without cardioplegia (p less than 0.01). The decrease in myocardial contractility demonstrated when no cardioplegic protection was employed (86% recovery) was completely eliminated (100% recovery) with a single-bolus infusion of cardioplegic solution containing glucose (p less 0.025). Intermittent infusions of cardioplegic solution containing glucose (92% recovery) and single infusions without glucose (93% recovery) also improved recovery of contractility following ischemia, but the results were not statistically significant.

Delayed recovery following hypothermic arrest in rabbit myocardium.

The purpose of this investigation was to determine the relationship between the duration of myocardial ischemia at 15 degrees C and the time required for the myocardium to recover maximum contractile function following the ischemia. The isolated blood perfused rabbit heart was used as a model of myocardial ischemia. Hearts from 22 New Zealand white rabbits were divided into four groups. In Group I seven hearts were subjected to 15 minutes of ischemia at 15 degrees C. In Group II five hearts were subjected to 30 minutes of ischemia at 15 degrees C. In Group III and IV the ischemia time was extended to 60 and 120 minutes, respectively. Following the ischemia each heart was reperfused at normothermia and papillary muscle contractility was measured and used as an index of myocardial recovery. Hearts in Group I recovered their maximum contractile function after an average of 22.5 minutes. Those in Groups II, III, and IV were fully recovered after 31.7, 38.2, and 45.5 minutes, respectively. The study indicates that the time required for the maximum recovery of myocardial contractility following myocardial ischemia increases at a decreasing rate with an increase in the duration of the ischemia at 15 degrees C.

Asymmetrical myocardial hypothermia during hypothermic cardioplegia.

To evaluate the possibility of inadequate right ventricular protection during operation, the temperatures of the anterior myocardium of the right ventricle and the middle of the interventricular septum were compared at ten-minute intervals throughout the period of continuous coronary ischemia in 130 consecutive patients. Systemic temperature was lowered to 23 degrees C, using cardiopulmonary bypass. Cardiac arrest was induced by aortic cross-clamping and infusion of cold cardioplegic solution. Cold solution was reinfused as necessary to maintain septal temperatures at less than 20 degrees C. Despite the use of superior and inferior vena caval cannulation for control of venous return, it was more difficult to maintain the right ventricle at the desired degree of myocardial hypothermia than the left ventricle. The difference between left and right ventricular temperatures was as great as 19 degrees C. In 80% of the observations (n = 1,010), the right ventricle was warmer than the left ventricle. The most frequently occurring temperature differences (left ventricle minus right ventricle) were in the 2 degrees to 3 degrees C range. These data indicate that it is more difficult to maintain hypothermia in the right ventricle. Concern for the left ventricle alone may be misleading. An alarming degree of rewarming may occur in the right ventricle and thereby contribute to right ventricular dysfunction and unilateral right ventricular failure.