Craig G. Hartford

Myocardial stiffness is attributed to alterations in cross-linked collagen rather than total collagen or phenotypes in spontaneously hypertensive rats.

BACKGROUND The relative contributions of increases in myocardial collagen, collagen cross-linking, and the ratio of type I to type III collagen to the stiff myocardium in hypertension were determined. METHODS AND RESULTS We compared the action of hydralazine (0.07 mmol x kg(-1) x d(-1)) with that of captopril (0.22 mmol x kg(-1) x d(-1)) on the left ventricular end-diastolic (LVED) myocardial stiffness constant, k (g x cm(-2)) and LV myocardial interstitial characteristics in spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) control rats. LVED k (SHR, 27.9+/-1; WKY, 19.5+/-1.2; P<.01), myocardial hydroxyproline concentrations (HPRO; microg/mg dry wt) (SHR, 4.19+/-0.16; WKY, 3.17+/-0.09; P<.001), and collagen type I/III ratios (SHR, 7.1+/-0.7; WKY, 2.1+/-0.2; P<.001) were increased, whereas the percentage of myocardial collagen extracted after cyanogen bromide digestion (an index of cross-linked collagen) was decreased (SHR, 17+/-3; WKY, 41+/-4; P<.001) in SHRs compared with WKY controls. Captopril therapy reduced LVED k, myocardial HPRO, collagen type I/III, and augmented collagen solubility (43+/-4) in SHRs to values similar to those measured in WKY controls. Hydralazine therapy, despite a favorable effect on LVED k in SHRs (20.+/-1.6, P<.01 compared with untreated SHRs), failed to influence either myocardial HPRO (4.18+/-0.18) or collagen type I/III (8+/-1) but did improve collagen solubility (31+/-2). CONCLUSIONS An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.

Lipoprotein (a) and cholesterol in body builders using anabolic androgenic steroids.

We examined the influence of self-administered anabolic androgenic steroids (AAS) on the lipogram of male body builders. Serum lipoprotein (a) (Lp(a)), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured in 10 experimental and 8 control male competitive body builders. The proportion of subjects with serum Lp(a) levels above 30 mg.dl-1 was significantly lower in the AAS group than the non-AAS group. HDL-C levels were significantly lower and LDL-C levels significantly higher in the AAS group than the non-AAS group. These data suggest that AAS in male body builders have a beneficial effect on serum Lp(a) levels but reduce the HDL-C:LDL-C ratio.

The agreement between reaction-board measurements and kinematic estimation of adult male human whole body centre of mass location during running

The segmental method for estimating the centre of mass (COM) location of the human body has been widely used since 1889. How closely this method agrees with direct measurements of the location and movement of COM during activity however, remains unclear. To test this, a novel reaction-board utilizing life sized projections of human subjects is designed for measuring COM location. Agreement between the segmental method and the more direct reaction-board measurement method is then assessed. Our data demonstrate that the reaction-board system has a physical maximum error of 1.28 cm and 1.95 cm for locating COM along the vertical (board length) and horizontal (board width) axes respectively, and show that the reaction-board and segmental methods agree to within limits of 6.0 cm for the location of COM and to within 5.6 cm for the movement of COM between two points, in recumbent individuals. Applied to running, the segmental method agrees to within limits of 4.8 cm for oscillation of COM and 5.3 cm for stride median COM height. The segmental method agrees with a more direct technique of known accuracy, the reaction-board method, most closely when measuring averaged oscillation over repeated strides, where it displays a measurement error range of 5.1 cm to 0.1 cm in runners.

Correctly selecting a liquid‐filled nasogastric infant feeding catheter to measure intraesophageal pressure

Polyvinyl chloride (PVC) nasogastric feeding catheters are used clinically to measure intraesophageal pressure as an estimate of pleural pressure for calculating lung compliance in infants. The accuracy of pressure measurement of 4 French gauge (FG) catheter sizes and three brands of liquid‐filled catheter manometer systems (CMS) was evaluated by determining their resonance‐frequency amplitude and phase properties. All CMS were underdamped and resonated. No CMS exhibited a uniform mean frequency response above 11 Hz. The maximum respiratory rate (Frr) within which CMS could potentially measure dynamic intraesophageal pressure within a 5% error limit was determined (Frr): the highest mean Frr recorded reliably in large‐diameter catheters was 82 breaths/min. Significant CMS differences in accuracy existed between catheter FG sizes and between catheters of similar diameters but differing brands. Correlation (r2) between catheter inner diameter and CMS Frr was 0.66 across brands. In conclusion, intraesophageal PVC liquid‐filled feeding catheters are suitable for estimating pleural pressure in subjects mechanically ventilated without sharp inspiratory waveforms or high respiratory rates. Quantitative frequency response characterization of different nasogastric catheter brands and different diameters is mandatory prior to their utilization. Pediatr. Pulmonol. 1997; 23:362–369.

Frequency responses of infant air-balloon versus liquid-filled catheters for intra-esophageal pressure measurement

Amplitude and phase frequency response characteristics of infant air‐balloon catheters (IABC) of differing French gauge (FG) sizes and brands were quantified to determine their suitability for measuring dynamic intra‐esophageal pressure (Pes) accurately. Frequency response performances of matching IABC and water‐filled catheters (WFC) were also compared using the swept sine wave technique. The maximum respiratory rate within which IABCs could potentially measure Pes within a 5% error limit was calculated (FRR).

Influence of ketanserin on regional myocardial blood flow after myocardial infarction in baboons.

Serotonin (5-hydroxytryptamine, 5-HT) mediates vasoconstriction and vasodilation in normal coronary circulation of various animal species. In the presence of coronary artery disease, serotonin may inhibit coronary collateral formation and stimulate predominantly vasoconstriction. We tested the effect of ketanserin, a selective 5-HT2 receptor antagonist and platelet aggregation inhibitor, on ischemic myocardium blood flow (BF) and collateral formation after coronary artery occlusion in primates. Fifteen baboons were subjected to left anterior descending coronary artery (LAD) ligation and thrombus formation. Hemodynamics and regional myocardial blood flow (RMBF) (microsphere technique) were measured before and 45 min and 1 week after coronary artery occlusion. There was no significant difference in the hemodynamic measurements, gross infarct size, or infarct-ischemic zone MBF in the experimental group (ketanserin 1 mg/kg daily, n = 9) as compared with the control group (injectable water, n = 6). Both groups had a significant increase in BF ratio of infarct-ischemic/ normal myocardium at 1 week as compared with shortly after coronary occlusion. Thus, selective 5-HT2 receptor blockade has neither an adverse nor a protective effect on myocardial infarct resulting from acute thrombotic coronary occlusion in baboons.

Primate pleuroesophageal tissue barrier frequency response and esophageal pressure waveform bandwidth in health and acute lung injury.

Background Dynamic intraesophageal pressure (Pes) is used to estimate intrapleural pressure (Ppl) to calculate lung compliance and resistance. This study investigated the nonhuman primate Ppl–Pes tissue barrier frequency response and the dynamic response requirements of Pes manometers. Methods In healthy monkeys and monkeys with acute lung injury undergoing ventilation, simultaneous Ppl and Pes were measured directly to determine the Ppl–Pes tissue barrier amplitude frequency response, using the swept-sine wave technique. The bandwidths of physiologic Pes waveforms acquired during conventional mechanical ventilation were calculated using digital low-pass signal filtering. Results The Ppl–Pes tissue barrier is amplitude-uniform within the bandwidth of conventional Pes waveforms in healthy and acute lung injury lungs, and does not significantly attenuate Ppl–Pes signal transmission between 1 and 40 Hz. At Pes frequencies higher than conventional clinical regions of interest the Ppl–Pes barrier resonates significantly, is pressure amplitude dependent at low-pressure offsets, and is significantly altered by acute lung injury. Allowing for 5% or less Pes waveform error, the maximum Pes bandwidths during conventional ventilation were 1.9 Hz and 3.4 Hz for physiologic and extreme-case waveforms in healthy lungs and 4.6 Hz and 8.5 Hz during acute lung injury. Conclusions In monkeys, the Ppl–Pes tissue barrier has a frequency response suitable for Ppl estimation during low-frequency mechanical ventilation, and Pes manometers should have a minimum uniform frequency response up to 8.5 Hz. However, the Ppl–Pes tissue barrier adversely affects the accurate estimation of dynamic Ppl at high frequencies, with varied airway pressure amplitudes and offsets, such as the Ppl encountered during high-frequency oscillatory ventilation.

Suitability of polyvinyl chloride feeding catheters in catheter manometer systems

Intra-pleural pressure is clinically estimated by measuring intra-esophageal pressure. The potential for three brands of four French Gauge (FG) size Polyvinyl chloride (PVC) fluid-filled catheter manometer systems (CMS) to measure intra-esophageal pressure accurately was quantified by determining their in vitro resonance frequency properties. All CMS were underdamped and resonated. No CMS exhibited a uniform mean frequency response above 11 Hz. Large FG catheters exhibited the potential to measure dynamic intra-esophageal pressure up to 82 breaths/min maximally within a 5% error limit. Significant differences in measurement accuracy existed between catheter FG sizes and between catheters of similar diameters but differing brands. In conclusion, in the absence of sharp inspiratory waveforms or high respiratory rates, intra-esophageal PVC catheters should accurately measure transmitted pleural pressures. Quantitative frequency response characterisation of various nasogastric catheter brands and sizes is desirable.

Frequency response of the pleuro-esophageal tissue barrier and esophageal pressure waveform bandwidth in non-human primates

Dynamic intra-esophageal pressure (Pes) is used to estimate intra-pleural pressure (Ppl) for calculating lung compliance. We quantified the amplitude frequency response required of Pes catheter manometers to reproduce Pes waveforms faithfully, and determined the amplitude frequency response of the Ppl-Pes tissue barrier using simultaneous Ppl and Pes measurements in mechanically ventilated monkeys. Allowing for 3% Pes waveform reproduction error, Pes end-inspiratory to end-expiratory pressure (/spl Delta/Ppk) was not significantly affected by filtering Pes at low-pass cut-off frequencies>the Pes fourth harmonic frequency. The Ppl-Pes tissue barrier had a near-uniform amplitude frequency response over the band of current clinical interest, but at a low airway pressure offset significant resonance occurred in the 32-40 Hz band. We conclude that to reproduce dynamic Pes waveforms faithfully Pes catheter manometers require amplitude frequency responses with uniformity up to the Pes fourth harmonic frequency. Transmission of high frequency components across the Ppl-Pes tissue barrier is subject to amplification. These findings have implications for measurements of lung compliance at high respiratory frequencies and varied airway pressure offsets.