The effect of high versus low loading on bone strength in middle life.

While bone mass and geometry are largely genetically determined, mechanical loading is considered to be an important additional determinant. This study investigates to what extent very high mechanical loading begun at a young age and sustained afterward can affect tibia bone mass and geometry in middle age. Cohorts from a common ethnic background, with a history of very high and very low tibia bone loading based on an assessment of their activities according their strain levels were compared. The study hypothesis was that the tibia bone density and geometric strength parameters would be greater in the high bone loading cohort. Subjects from a group of elite infantry recruits who sustained a 31% incidence of stress fractures during their basic training in 1983, were reviewed 25 years later. The tibia bone strength of 25 of these soldiers, 11 of whom had sustained stress fractures, was compared to a group of 20 subjects who received exemption from military service in 1982-5 because they were religious scholars and who continued these studies afterwards. Anthropometric measurements were made. The bone density and geometric strength of the tibia was assessed by quantitative computerized tomography (QCT). The average daily dietary intake and metabolic expenditure of subjects were assessed by questionnaires. At the 25 year follow-up soldiers were on an average 3 cm taller than the religious scholars (p=0.02) and had lower abdominal girths (p=0.03). There was no difference in the tibia cortical density between cohorts in spite of the fact that the religious scholars had lower daily calcium intakes (p=0.02). Soldiers had stronger tibias based on geometric engineering criteria. The mean area moments of inertia (p=0.02, p=0.04) and polar moments of inertia (p=0.02) were 16% larger in the soldier cohort. By multivariate regression analysis greater height, weight and daily energy expenditure were related to larger bone geometric strength parameters. According to semipartial eta-square analysis, between 39% to 45% of the variance in the area moments of inertia between the cohorts was attributable to these three parameters. The religious scholars burned less calories daily, principally because they did no sport activity (p=0.001). There was no difference in tibia bone strength parameters between soldiers who did and did not sustain stress fractures in their 1983 basic training. In conclusion, in a middle age population with a common ethnic origin, the high bone loading cohort had stronger tibias than the low bone loading cohort based on larger geometric strength properties and not because of higher cortical density. In spite of being at the extremes of the bone loading spectra, the tibia area moment of inertia of the two cohorts in this study differed by only 16%, with part of this difference attributable to factors other than bone loading. We do not know for sure if the difference in the geometric properties is related to high bone loading or whether people with stronger bones are more likely to engage in high bone loading. Healthy male subjects who sustained stress fractures at a young age do not have weaker tibias at middle age according to QCT measurements.

Role of nitric oxide and TPEN, a potent metal chelator, in ischaemic and reperfused rat isolated hearts.

1. The role of nitric oxide (NO) was studied in the control of ischaemic/reperfused cardiac function and the effect of N,N,N',N'-tetrakis-[2-pyridylmethyl]-ethylenediamine (TPEN), a potent metal chelator, on the regulation of cardiac NO formation. 2. Rat isolated working hearts were subjected to 30 min ischaemia and reperfusion. The incidence of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT) and the recovery of cardiac function were measured. Nitric oxide was detected by electron spin resonance (ESR) spectroscopy. 3. With 5.0, 7.5 and 10.0 mumol/L of TPEN administered prior to ischaemia, the drug produced a reduction in the incidence of VF from its control value of 100% to 25% (P < 0.05), 17% (P < 0.05) and 8% (P < 0.05), respectively. The incidence of VT followed the same pattern. 4. When TPEN was given at the moment of reperfusion, a reduction in the incidence of VF and VT was still observed. Reduction in the incidence of VF and VT was reflected in the improvement of cardiac function both in the pre- and post-ischaemic TPEN-treated groups. 5. TPEN reduced basal cardiac NO content and prevented the accumulation of NO during ischaemia/reperfusion. 6. The results show that TPEN exerts beneficial effects on postischaemic cardiac function and dysrhythmias in relation to inhibition of the accumulation of NO in ischaemic/reperfused myocardium.

New experimental technique to study blood cardioplegia in the isolated, perfused rat heart.

Blood cardioplegia has been extensively studied clinically and in the large animal experimental model. We describe here a modification of the original Langendorff technique to study continuous warm blood cardioplegia in the isolated, perfused rat heart. The excised heart is mounted on the perfusion apparatus and perfused with Krebs-Henseleit buffer. Prearrest hemodynamics are recorded. The shed blood in the mediastinal cavity (8 to 12 mL) is collected, filtered, and reconstituted into cardioplegic solution (hematocrit, 0.20; K+, 15 mmol/L). Hearts are arrested and maintained at 37 degrees C by continuous recirculation of blood cardioplegia for 1 hour. The blood cardioplegia system consists of a Silastic tubing oxygenator, peristaltic pump, and two filters (40 microns pore size). The heart is reperfused with Krebs-Henseleit solution, and postarrest hemodynamics are recorded. Percentage recovery of peak left ventricular pressure, heart rate, and coronary flow were 98.5 +/- 3.1, 102 +/- 4.2, and 98.5 +/- 4.5 (mean +/- standard error of the mean; n = 6), respectively. Myocardial oxygen consumption during arrest was 57 microL.min-1.g-1 dry wt, which is 10% of the myocardial oxygen consumption of a beating heart in in-vivo and ex-vivo models. These results suggest the feasibility of studying blood cardioplegia in the isolated, perfused rat heart model under controlled conditions. Continuous warm blood cardioplegic arrest provided excellent myocardial protection for 1 hour in this model.

TPEN, a transition metal chelator, improves myocardial protection during prolonged ischemia.

In view of the hypothesis that free radicals induced damage during ischemia and reperfusion is mediated by transition metals, we investigated the effect of the potent metal chelator TPEN (N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine) on cardiac function after prolonged myocardial ischemia. Isolated working rat hearts were subjected to 12 hours of cold ischemic arrest followed by reperfusion for 1 hour. The study was carried out on five groups (nine hearts in each): (1) St. Thomas' Hospital cardioplegic solution; (2) St. Thomas' Hospital cardioplegic solution with 7.5 mumol/L TPEN; (3) protection conditions as in group 2, but with TPEN administration during preischemic and reperfusion periods; (4) University of Wisconsin solution; and (5) the same conditions as in group 4 with TPEN administration during the preischemic and reperfusion periods. Significant enhancement of hemodynamic recovery was observed in the presence of TPEN throughout the experiment. The recovery of cardiac output was 24% +/- 4% in group 3, as compared to 12% +/- 4% in group 1 (p < 0.01). The postischemic left ventricular pressure recovery was 57% +/- 4% in group 3, as compared to 18% +/- 7% in group 1 (p < 0.005). The hearts in group 5 recovered, reaching 29% +/- 2% of the preischemic cardiac output and at 65% +/- 2% of the left ventricular pressure recovery (p < 0.05 versus group 3). Lactate dehydrogenase was released throughout the reperfusion. TPEN addition to groups 2 and 3 did not significantly reduce lactate dehydrogenase release; however, TPEN in University of Wisconsin solution and throughout the experiment significantly decreased lactate dehydrogenase release.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of swimming exercise on spontaneous ventricular defibrillation and ventricular fibrillation threshold in the isolated perfused rat heart.

Effects of swimming exercise training on left ventricular contraction and relaxation, the incidence of spontaneous defibrillation and the ventricular fibrillation threshold were studied in the isolated, perfused rat heart. The heart/body weight ratio was 4.8 +/- 0.4 x 10(-3) in swimmers compared with 3.9 +/- 0.6 x 10(-3) in sedentary controls (p less than 0.0005). The spontaneous heart rate was lower in isolated hearts of trained animals (222 +/- 18 bpm compared with 244 +/- 28, p less than 0.05). Left ventricular systolic pressure was higher in trained hearts and the rate of ventricular relaxation enhanced (p less than 0.05). The ventricular fibrillation threshold was 7.2 +/- 5.2 and 10.8 +/- 6.1 mamp in hearts of swimmers and controls, respectively, the difference not being significant. The incidence of spontaneous defibrillation was not significantly different between the two groups. It is concluded that, while swimming induces cardiac hypertrophy and hemodynamic changes, it neither protects against the induction of ventricular fibrillation nor facilitates spontaneous defibrillation in the isolated, non-ischemic rat heart.

Long-term evaluation of a new selectively biodegradable vascular graft coated with polyethylene oxide-polylactic acid for right ventricular conduit. An experimental study.

Low-porosity woven Dacron grafts have been used extensively as an extracardiac conduit in the surgical treatment of congenital and acquired heart diseases involving total heparinization. Caution is still warranted in their use, however, because of long-term complications, including calcification and development of obstructive fibrous peel. In contrast, high-porosity grafts offer much better tissue anchorage and healing but cannot be used under heparinization. We have developed a compound vascular prosthesis in which a knitted Dacron graft is coated with a polymeric biodegradable sealant. Polyethylene oxide-polylactic acid-segmented copolymers comprised the degradable component of the graft. In vitro studies showed that the coated prosthesis exhibited a highly flexible elastomer-like mechanical response. The prostheses were completely watertight, and significant degradation started after 1 week, with absorption completed after 3 weeks. Seven woven and six knitted polyethylene oxide-polylactic acid-coated Dacron grafts used as extracordiac conduits (16 mm), connecting the right ventricle and the pulmonary artery were implanted in dogs. The dogs were killed after 12 to 18 months, and the results are reported. Scanning electron microscopy examination showed peel detachment and nonhomogenous intimal surface with fenestrations in the woven graft group, but complete healing and incorporation of the pseudointima with homogenous, thin lining of the luminal surface in the polyethylene oxide-polylactic acid-coated group. Histologic studies indicated much superior healing and anchorage of the periprosthetic tissue and the pseudointima in the polyethylene oxide-polylactic acid-coated grafts. The biodegradable polymer was fully degraded and exhibited a complete incorporation of the compound vascular prosthesis. This study indicates the superior healing properties of these selectively biodegradable grafts, which might increase long-term patency and decrease complications of right ventricular conduits.

Protective effect of branched chain-enriched amino acid formulation in myocardial ischemia.

The protective effect of a branched chain amino acid (BCAA) formulation on the ischemic myocardium was determined in four groups of passively perfused normothermic (37 C) isolated rat hearts perfused with Krebs-Henseleit (KH) or KH + BCAA. Time to ischemic contracture was significantly increased by the infusion of BCAA compared with KH (19.4 +/- 2.3 vs. 15.9 +/- 1.7 min). In a second set of experiments, rat hearts were perfused with KH or KH + BCAA solution followed by 2 min of glucose-free KH buffer. After 17 min of ischemia, both groups were reperfused for another 15 min. Percent of pressure recovery was significantly better with KH + BCAA (90.1 +/- 8.4) than with KH (56.4 +/- 40.0). Percent +dP/dt (time derivative of pressure at contraction) recovery was also significantly improved with KH + BCAA (96.5 +/- 26.9 vs. 58.1 +/- 44.0). Furthermore, arrhythmias were minimized by BCAA. There was no difference in change of coronary flow between these two groups. Thus, BCAAs appear to protect the heart against myocardial ischemic injury and to delay the time to ischemic contracture, particularly in the depleted ischemic heart. BCAAs enhance postischemic pressure recovery and improve postischemic systolic and diastolic myocardial function.

Biodegradable PELA block copolymers: in vitro degradation and tissue reaction.

Degradation of, and tissue reaction elicited by a series of polyethylene oxide (PEO)/polylactic acid (PLA) PELA block copolymers were studied in vitro and in vivo. In particular, the effect of pH, temperature and enzymatic activity was addressed. The mass loss was faster, the more basic the media, while, expectedly, PELA copolymers degraded faster with the higher temperature. The addition of an enzyme (carboxylic ester hydrolase) had no effect. The degradation process strongly affected the mechanical properties of the materials under investigation, the elongation at break dropping drastically after two days of degradation. After seven days, only gross observation of the extensively degraded samples was possible. The in vivo studies compared the tissue reaction elicited by various PELA copolymers to that evoked by PLA. Evaluation of tissue reaction observed with a PELA sample after sterilization with gamma radiation showed acute inflammation with considerable dispersion of the material, 12 days after implantation. The granulomatous reaction observed with PELA copolymers after ethylene oxide sterilization was identical to the reaction observed with PLA.

Pericardial meshing: an effective method for prevention of pericardial adhesions and epicardial reaction after cardiac operations.

Cardiac reoperations, particularly for coronary revascularization, are becoming more frequent and carry increased risk of damage to the heart during resternotomy. We experimentally evaluated a pericardial meshing technique to facilitate primary pericardial closure. In 18 mongrel dogs, an 8 by 5 cm pericardial flap was fashioned through a left thoracotomy. A standardized procedure for induction of pericardial adhesions was carried out in all animals. Animals were divided into three groups of six animals each: Group I (control)--the pericardial flap was primarily resutured; Group II--the flap was meshed and then resutured; and Group III--the flap was replaced by a pericardial substitute. Animals were put to death 8 weeks postoperatively and the pericardial space was examined for adhesions and epicardial reaction. The extent of adhesions and epicardial reaction was graded as: 0--none; 1--minimal; 2--moderate; and 3--severe. Both in Group I and Group III severe pericardial adhesions (grade 2-3) and epicardial reactions (grade 2-3) were formed, which obscured the underlying coronary anatomy. In Group II pericardial adhesions and epicardial reactions were none to minimal (grade 0-1) and the underlying coronary anatomy was not obscured. The meshed pericardium was completely regenerated by normal pericardium within several weeks. This study demonstrates that pericardial meshing facilitates primary tension-free pericardial closure. Free drainage of intrapericardial blood is achieved. A complete anatomic layer between heart and sternum is restored. Pericardial meshing is superior to the pericardial substitutes examined, as adhesions and epicardial reactions are significantly reduced, and the coronary anatomy is readily identifiable.