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Biomedical subjects

G M Kent

Publications and source records attributed to G M Kent.

At least 19 recordsLinked to original sources

Long-term evolution of cardiomyopathy in dialysis patients.

BACKGROUND: Left ventricular enlargement is very common at the inception of dialysis therapy, and highly predictive of future cardiac morbidity and mortality. It is not known whether cardiac size increases further while on dialysis therapy and whether potentially reversible risk factors for later progression can be identified. METHODS; Baseline and yearly echocardiograms were performed in a prospective inception cohort of 433 dialysis patients. The mean patient follow-up was 41 months; 29 patients had four consecutive echocardiograms at yearly intervals. RESULTS: The patient subset with four echocardiograms was older (58 vs. 51 years, P = 0.02) and had a lower mass ventricular mass index (128 vs. 149 g/m2, P = 0.02) than the parent group. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive increases over time in posterior wall thickness (P = 0.015), left ventricular end-diastolic diameter, left ventricular mass index (P = 0.001), and cavity volume index (P = 0. 001). Mass-to-volume ratios did not change. The biggest changes in mass (18 g/m2 - 14%)and volume index (13 ml/m2 - 18%) occurred between baseline and year 1, although increases in both were seen after year 1. Hemodialysis versus peritoneal dialysis (41 g/m2, P = 0.008) and anemia (10 g/m2 per 1 g/dl drop in hemoglobin, P = 0.02) were associated with progressive left ventricular enlargement, but only within the first year of dialysis therapy. The left ventricular enlargement seen after year 1 was independent of anemia, blood pressure, serum albumin and mode of dialysis. CONCLUSIONS: Progressive cardiac enlargement, particularly left ventricular dilation with compensatory hypertrophy, continues after starting dialysis therapy. Most of the additional cardiac enlargement seems to occur in the first year of dialysis therapy, suggesting that intervention beyond one year may be relatively ineffective.

Blood Pressure

Mode of dialysis therapy and mortality in end-stage renal disease.

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of 433 end-stage renal disease patients was followed prospectively for a mean of 41 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo. After adjustment for PD patients less likely to have chronic hypertension and more likely to have diabetes, ischemic heart disease, and cardiac failure at baseline (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there was no statistically significant difference in mortality. After 2 yr, mortality was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95% confidence interval [CI], 0.97 to 2.53). Both the occurrence (adjusted hazards ratio 6.87 [95% CI, 2.01 to 23.5]) and the direction (toward PD, adjusted hazards ratio 6.25 [95% CI, 1.54 to 25]) of a therapy switch were subsequently associated with mortality after 2 yr. Progressive clinical and echocardiographic cardiac disease were not responsible for this late mortality. Lower mean serum albumin levels in PD patients in the first 2 yr of therapy (3.5 +/- 0.5 versus 3.9 +/- 0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in subsequent mortality. Hemodialysis has a late survival advantage over peritoneal dialysis; antecedent hypoalbuminemia is a major marker of the increased late mortality in PD patients.

Adult

Cardiac disease in diabetic end-stage renal disease.

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38%, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18%, p = 0.003) and cardiac failure (48 vs 24%, p < 0.00001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia.

Adult

The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease.

To determine the possible association between anemia and clinical and echocardiographic cardiac disease, a cohort of 432 end-stage renal disease patients (261 on hemodialysis and 171 on peritoneal dialysis) who started dialysis therapy between 1982 and 1991 were followed prospectively for an average of 41 months. Baseline demographic, clinical, and echocardiographic assessments were performed, as well as monthly serial clinical and laboratory tests while the patients were on dialysis therapy. The mean (+/-SD) hemoglobin level during dialysis therapy was 8.8 +/- 1.5 g/dL. After adjusting for age, diabetes, and ischemic heart disease, as well as for blood pressure and serum albumin levels measured serially, each 1 g/dL decrease in mean hemoglobin was independently associated with the presence of left ventricular dilatation on repeat echocardiogram (odds ratio, 1.46; P = 0.018) and the development of de novo (relative risk [RR] = 1.28; P = 0.018) and recurrent (RR = 1.20; P = 0.046) cardiac failure. In addition, each 1 g/dL decrease in the mean hemoglobin level was independently associated with mortality while the patients were on dialysis therapy (RR = 1.14; P = 0.024). Anemia had no independent association with the development of ischemic heart disease while the patients were on dialysis therapy. Anemia, an easily reversible feature of end-stage renal disease, is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality in end-stage renal disease patients.

Anemia

Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed prospectively for an average of 41 months. Baseline and annual demographic, clinical and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while on dialysis therapy. The average mean arterial blood pressure level during dialysis therapy was 101 +/- 11 mm Hg. After adjusting for age, diabetes and ischemic heart disease, as well as hemoglobin and serum albumin levels measured serially, each 10 mm Hg rise in mean arterial blood pressure was independently associated with: the presence of concentric LV hypertrophy (OR 1.48, P = 0.02), the change in LV mass index (beta = 5.4 g/m2, P = 0.027) and cavity volume (beta = 4.3 ml/m2, P = 0.048) on follow-up echocardiography, the development of de novo cardiac failure (RR 1.44, P = 0.007), and the development of de novo ischemic heart disease (RR 1.39, P = 0.05). The association with LV dilation was of borderline statistical significance (OR 1.48, P = 0.06). Mean arterial blood pressures greater than 106 mm Hg were associated with both echocardiographic and clinical endpoints. Paradoxically, low mean arterial blood pressure (RR 1.36 per 10 mm Hg fall, P = 0.009) was independently associated with mortality. The association of low blood pressure with mortality was a marker for having had cardiac failure prior to death. We conclude that even moderate hypertension worsens the echocardiographic and clinical outcome in ESRD patients, especially in those without previous clinical cardiac disease.

Adult

Outcome and risk factors of ischemic heart disease in chronic uremia.

To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals. Twenty-two percent of patients (N = 95) had either a history of angina pectoris or myocardial infarction on starting dialysis therapy. Median time to onset of heart failure was 24 months in those with ischemic heart disease on initiation of dialysis, compared to 55 months in those without (P < 0.0001). This effect was independent of age, diabetes and underlying cardiomyopathy. Median survival was 44 months in those with ischemic disease compared to 56 months in those without (P = 0.0001). This adverse impact was independent of age and diabetes mellitus but, when cardiac failure was added to the Cox's model, ischemic heart disease was no longer an independent predictor of survival. De novo ischemic heart disease, not evident on starting dialysis therapy, occurred in 41 (9%) patients. When compared to patients who never developed ischemic disease (N = 296; 69%), significant and independent predictors of de novo disease were older age (P = 0.0007), diabetes mellitus (P = 0.0001), high blood pressure during follow up on dialysis (P = 0.02) and hypoalbuminemia (P = 0.03), whereas anemia was not an independent predictor. LV mass index was 174 +/- 7 g/m2 in those who developed de novo ischemic disease compared to 155 +/- 3 g/m2 (P < 0.001) in those who did not. Concentric LV hypertrophy, LV dilation and systolic dysfunction were independent risk factors for de novo ischemic heart disease. We conclude that ischemic heart disease occurs frequently in dialysis patients, that its adverse impact is mediated through the development of heart failure, and that the most important, potentially reversible risk factors are hypertension, hypoalbuminemia, and underlying cardiomyopathy.

Adult

Hypocalcemia, morbidity, and mortality in end-stage renal disease.

BACKGROUND: Hypocalcemia and hyperphosphatemia with secondary hyper-parathyroidism are characteristic of end-stage renal disease (ESRD). Although calcium levels critically affect almost all cellular processes, the impact of chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on the prognosis of ESRD patients is unknown. METHODS: An inception cohort of 433 patients starting ESRD therapy was followed prospectively for an average of 41 months. Serum calcium and other parameters were measured monthly. The mean calcium levels were 9.4 +/- 0.7 mg/dl. 23% of the patients had mean calcium levels < 8.8 mg/dl. After adjusting for baseline age, diabetes mellitus, ischemic heart disease, smoking and cholesterol levels, as well as serial albumin, hemoglobin, mean arterial blood pressure, phosphate and alkaline phosphatase levels, chronic hypocalcemia was strongly associated with mortality (RR 2.10, p = 0.006 for a mean calcium level < 8.8 mg/dl). The association with mortality was similar in hemodialysis (RR 2.10, p = 0.006) and peritoneal dialysis patients (2.67, p = 0.034). Using similar covariate adjustment, chronic hypocalcemia was associated with de novo ischemic heart disease (RR 5.23, p < 0.001), recurrent ischemic heart disease (RR 2.46, p = 0.006), de novo cardiac failure (RR 2.64, p < 0.001), and recurrent cardiac failure (RR 3.30, p < 0.001). Hypocalcemia retained its independent impact on morbidity and mortality when analyzed as a time-dependent covariate. CONCLUSIONS: Chronic hypocalcemia, a very common, reversible feature of chronic uremia, is independently associated with morbidity and mortality in ESRD patients.

Alkaline Phosphatase

Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed up prospectively for an average of 41 months. Baseline and annual demographic, clinical, and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while patients were on dialysis therapy. Among hemodialysis patients, after adjustment was made for age, diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure levels measured serially, a 10-g/L fall in mean serum albumin level was independently associated with the the development of de novo (relative risk [RR], 2.22; P = 0.001) and recurrent cardiac failure (RR, 3.84; P = 0.003), de novo (RR, 5.29; P = 0.001) and recurrent ischemic heart disease (RR, 4.24; P = 0.005), cardiac mortality (RR, 5.60; P = 0.001), and overall mortality (RR, 4.33; P < 0.001). Among peritoneal dialysis patients, a 10-g/L fall in mean serum albumin level was independently associated with the progression of left ventricular dilation as seen on follow-up echocardiography (beta, 13.4 mL/m2; P = 0.014), the development of de novo cardiac failure (RR, 4.16; P = 0.003), and overall mortality (RR, 2.06; P < 0.001). Hypoalbuminemia, a major adverse prognostic factor in dialysis patients, is strongly associated with cardiac disease.

Adult

Outcome and risk factors for left ventricular disorders in chronic uraemia.

BACKGROUND: Left ventricular disease occurs frequently in dialysis patients. It may be manifest as concentric LV hypertrophy, LV dilatation with or without LV hypertrophy, or systolic dysfunction. Little is known concerning the clinical outcome and risk factors for these disorders. METHODS: A cohort of 432 end-stage renal disease patients who survived at least 6 months had an echocardiogram on initiation of dialysis therapy. Clinical, laboratory and echocardiographic data was obtained annually during follow-up. RESULTS: On initiation of ESRD therapy 16% of patients had systolic dysfunction, 41% concentric LV hypertrophy, 28% LV dilatation, and only 16% had normal echocardiograms. Median time to development of heart failure was 19 months in patients with systolic dysfunction, 38 months in concentric LV hypertrophy and 38 months in LV dilatation. The relative risks of heart failure in the three groups were significantly worse than in the normal group, after adjusting for age, diabetes and ischaemic heart disease. Median survival was 38 months in systolic dysfunction, 48 months in concentric hypertrophy, 56 months in LV dilatation, and >66 months in the normal group. Two hundred and seventy-five patients had a follow-up echocardiogram 17 months after starting dialysis therapy together with serial measurement of potential risk factors prior to the echocardiogram. On follow-up echocardiogram the degree of concentric LV hypertrophy was independently related to hypertension while on dialysis, older age, and anaemia while on dialysis; the degree of LV dilatation was related to ischaemic heart disease, anaemia, hypertension and hypoalbuminemia while on dialysis; the degree of systolic dysfunction was associated with ischaemic heart disease and anaemia during follow-up. CONCLUSIONS: Manifestations of left ventricular disease are frequent and persistent in chronic uraemia, and are associated with high risks of heart failure and death. Potentially reversible risk factors include anaemia, hypertension, hypoalbuminaemia and ischaemic heart disease.

Adult

Impact of renal transplantation on uremic cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

Adult

Cardiac function and hematocrit level.

Patients on dialysis have an age-adjusted death rate 3.5 times that of the general population. The most common cause of death in patients on dialysis is cardiovascular disease. We prospectively followed a cohort of 433 patients in three centers for a mean of 41 months. Mean hemoglobin level at the beginning of dialysis was 8.39 (+/- 1.7) g/dL, and the mean hemoglobin level during follow-up was 8.84 (+/- 1.5) g/dL. Using Cox's regression model, we found that anemia predicted mortality independently of age, diabetes mellitus, cardiac failure, hypoalbuminemia, serum creatinine, mean arterial pressure, or echocardiographic heart disease. The independent relative risk (RR) of mortality was 1.18 per 1.0 g/dL decrease in hemoglobin level. Anemia also independently predicted the de novo occurrence of congestive heart failure when the same covariates were controlled for (RR, 1.49 per 1.0 g/dL decrease). Anemia was also independently predictive of heart failure at the start of dialysis (RR, 1.14 per 1.0 g/dL decrease) and heart failure recurrence (RR, 1.25 per 1.0 g/dL decrease). Left ventricular hypertrophy is present in 75% of patients on dialysis at the start of therapy for end-stage renal disease. It independently predicts mortality. Our prospective cohort study identified increasing age, hypertension, and anemia as risk factors for its development. One controlled study and several uncontrolled studies demonstrated improvement (but not complete regression) of elevated left ventricular mass in patients on dialysis treated with recombinant human erythropoietin (epoetin).

Cause of Death

Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors.

Cardiovascular disease is the most common cause of death in dialysis subjects. Congestive heart failure (CHF) is a common presenting symptom of cardiovascular disease in the dialysis population. Information regarding prevalence, incidence, risk factors and prognosis is crucial for planning rational interventional studies. A prospective multicenter cohort study of 432 dialysis patients followed for a mean of 41 months was carried out. Prospective information on a variety of risk factors was collected. Annual echocardiography and clinical assessment was performed. Major endpoints included death and the development of morbid cardiovascular events. One hundred and thirty-three (31%) subjects had CHF at the time of initiation of dialysis therapy. Multivariate analysis showed that the following risk factors were significantly and independently associated with CHF at baseline: systolic dysfunction, older age, diabetes mellitus and ischemic heart disease. Seventy-six of 299 subjects (25%) who did not have baseline CHF subsequently developed CHF during their course on dialysis. Compared to those subjects who never developed CHF (N = 218) multivariate analysis identified the following risk factors for the development of CHF: older age, anemia during dialysis therapy, hypoalbuminemia, hypertension during dialysis therapy, and systolic dysfunction. Seventy-five of the 133 (56%) subjects with CHF at baseline had recurrent CHF during follow-up. Independent and significant risk factors for CHF recurrence were ischemic heart disease and systolic dysfunction, anemia during dialysis therapy and hypoalbuminemia. The median survival of subjects with CHF at baseline was 36 months compared to 62 months in subjects without CHF. In this study the prevalence of CHF on starting ESRD therapy and the subsequent annual incidence was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

Clinical and echocardiographic disease in patients starting end-stage renal disease therapy.

End-stage renal disease (ESRD) patients have a high cardiovascular mortality rate. Precise estimates of the prevalence, risk factors and prognosis of different manifestations of cardiac disease are unavailable. In this study a prospective cohort of 433 ESRD patients was followed from the start of ESRD therapy for a mean of 41 months. Baseline clinical assessment and echocardiography were performed on all patients. The major outcome measure was death while on dialysis therapy. Clinical manifestations of cardiovascular disease were highly prevalent at the start of ESRD therapy: 14% had coronary artery disease, 19% angina pectoris, 31% cardiac failure, 7% dysrhythmia and 8% peripheral vascular disease. On echocardiography 15% had systolic dysfunction, 32% left ventricular dilatation and 74% left ventricular hypertrophy. The overall median survival time was 50 months. Age, diabetes mellitus, cardiac failure, peripheral vascular disease and systolic dysfunction independently predicted death in all time frames. Coronary artery disease was associated with a worse prognosis in patients with cardiac failure at baseline. High left ventricular cavity volume and mass index were independently associated with death after two years. The independent associations of the different echocardiographic abnormalities were: systolic dysfunction-older age and coronary artery disease; left ventricular dilatation-male gender, anemia, hypocalcemia and hyperphosphatemia; left ventricular hypertrophy-older age, female gender, wide arterial pulse pressure, low blood urea and hypoalbuminemia. We conclude that clinical and echocardiographic cardiovascular disease are already present in a very high proportion of patients starting ESRD therapy and are independent mortality factors.

Cohort Studies

The prognostic importance of left ventricular geometry in uremic cardiomyopathy.

The objective of this study was to determine the effect of left ventricular (LV) mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients. The Design was a multicenter, prospective inception cohort study with a median follow-up of 41 months. The Setting was three university-affiliated nephrology units. A total of 433 patients who (1) survived > 6 months from the start of ESRD therapy and (2) had a technically satisfactory baseline echocardiogram were studied. Measurements included a baseline clinical, laboratory and echocardiographic assessment. LV hypertrophy was present in 74% and LV dilation was present in 36% of patients. In patients with normal cavity volume (< or = 90 mL/m2) and normal systolic function, high LV mass index (> 120 g/m2) and mass-to-volume ratios (> 2.2 g/mL) were independently associated with late mortality (> 2 yr after starting dialysis therapy). After adjusting for baseline age, diabetes, and ischemic heart disease, the relative risk for the former was 3.29 and for the latter was 2.24. Cavity volume was of no prognostic significance in this group. In patients with LV dilation and normal systolic function, high cavity volume (> 120 mL/m2) and low mass-to-volume ratio (< 1.8 mL/m2) were independently associated with late mortality, the relative risk in the former being 17.14 and the latter being 4.27. LV mass index was of no prognostic significance in this group. The baseline echocardiographic classification, based on LV mass and cavity volume, was the strongest predictor of late mortality, after adjusting for age, gender, diabetes mellitus, coronary artery disease, angina pectoris, chronic hypertension, and hemoglobin and serum albumin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Risk factors for the development of left ventricular hypertrophy in a prospectively followed cohort of dialysis patients.

The objective of this study was to determine the role of hypertension, age, anemia, and hyperparathyroidism in the pathogenesis of left ventricular hypertrophy (LVH) developing after the initiation of dialysis for ESRD. A cohort of dialysis patients who were being treated for ESRD and whose initial echocardiograms after the start of dialysis therapy do not show LVH were studied. Three hundred and thirty-nine patients have been monitored at three centers since 1985. Serial echocardiograms have been performed with M-mode and two-dimensional echocardiography. Data on blood pressure, height, weight, hemoglobin, number and type of antihypertensive medications, and the presence of functioning vascular access have been collected prospectively. Prospective data on serum calcium, serum phosphorus, alkaline phosphatase, and parathyroid hormone levels and skeletal x-rays have also been collected. By the use of set criteria and blinding to echocardiographic outcome, the presence and severity of hyperparathyroidism were graded by consensus. Fifty-one patients met eligibility criteria for inclusion; of these, 14 developed LVH (cases) and 37 did not (controls). Cases had significantly higher systolic blood pressure (P = 0.009) and were older (P = 0.01) than controls. Systolic blood pressure correlated significantly with final posterior left ventricular wall thickness (r = 0.39; P < 0.01). By the use of multivariate analysis, age and systolic blood pressure were significantly and independently associated with increased left ventricular mass index. The frequency of hyperparathyroidism was low and equal in both groups. There was a trend toward more severe anemia in cases that did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Age-related differences in the response to myocardial ischemic stress.

Clinical experience indicates that the risk of reparative cardiac operations is increased in the neonatal period relative to that in older infants and children. Age-related differences in the susceptibility to myocardial ischemic dysfunction were evaluated by comparison of left ventricular function and metabolism in neonatal (mean age = 7 days) and weanling (mean age = 96 days) piglets. Six animals in each group supported on cardiopulmonary bypass were subjected to (1) 120 minutes of hypothermic crystalloid cardioplegic arrest (CP-120) and (2) 15 minutes of normothermic ischemic arrest (NA-15) after a 60 minute interval of reperfusion. Left ventricular systolic and diastolic function was measured after each intervention via endocardially implanted ultrasonic dimension crystals in a septolateral minor-axis position. In both groups, systolic dysfunction was evidenced by an increase in the dimension-axis intercept (p = 0.001), but not the slope of the end-systolic pressure-dimension relation. Left ventricular end-diastolic stiffness, expressed as left ventricular end-diastolic pressure versus Lagrangian strain, increased to a similar degree in both groups (p = 0.001). Adenosine triphosphate levels declined significantly (p = 0.001) in both groups in response to the ischemic interventions with no evident intergroup differences. Lactate levels increased significantly during the course of the experiment (p = 0.04); however, the increases were greater (p = 0.009) at all intervals in the neonatal group. This study demonstrates age-related metabolic differences in response to ischemia consistent with a greater dependence on glycolysis in neonatal myocardia. However, the fact that discriminating age-related differences in left ventricular function were not evident suggests that factors other than young age per se account for the increased surgical mortality in the neonatal period.

Adenosine Triphosphate

The effect of porous surface configuration on the tensile strength of fixation of implants by bone ingrowth.

In an attempt to gain information that could be directly applied to the design of clinical porous-surfaced prostheses intended for biological attachment by bone ingrowth, the tensile strength of the bone-implant interface was expressed as a function of 2 fundamentally different porous-surface configurations. Using powder metallurgy techniques, standard 3-hole fracture fixation plates were prepared with both a single and a multiple layer of spherically shaped metal powder particles on the bone-contacting surface to produce implants with different porous surfaces. These plates were implanted onto the lateral aspect of canine femurs for periods of 4, 6, 8, 12, 18, and 24 weeks. Mechanical tests were performed to measure the tensile strength of fixation of the implants by the ingrowth of bone. The results of the mechanical tests indicated that implants with the multiple particle layer surfce configuration develop a greater tensile strength of fixation than do implants with the single particle layer surface configuration. In addition, this fixation strength develops more quickly if the cortical bone is petaled prior to implantation. These findings should be considered when designing porous-surfaced implants intended for fixation by bone ingrowth.

Animals

Perfusion of malignant hyperthermia susceptible and normal isolated pig livers with halothane.

We have perfused malignant hyperthermia susceptible and normal isolated pig livers with halothane for one hour. The liver temperatures, oxygen and carbon dioxide tensions, the base deficits and lactate concentrations in blood entering and leaving the liver have been measured at the beginning and at the end of the perfusion. Statistical analysis has shown that there are no significant differences in these parameters between the beginning and the end of the perfusion period or between the normal and the malignant hyperthermia susceptible livers. We conclude, therefore, that the livers of malignant hyperthermia susceptible pigs are either normal or else, if abnormal, the abnormalities are sufficiently benign as to be not measurably expressed.

Anesthesia, Inhalation