In vitro contractile properties of the diaphragm were measured in four groups of inbred adult hamsters (greater than 40wk), randomly divided into sedentary control (SC), exercise control (EC), sedentary emphysematous (SE), and exercise emphysematous (EE) groups. Emphysema was induced by a single endotracheal instillation of elastase. Exercise consisted of running 1 h/day, 7 days/wk for 20 wk. Functional residual capacity (FRC), measured by means of a pressure box, was approximately 2.5 times greater in both emphysematous groups compared with control groups. Small diaphragmatic bundles were then isolated and subjected to in vitro analysis of isometric contractile properties. No differences were observed among the four groups in time to peak tension, half-relaxation time, and shape of the force-frequency curve. The diaphragmatic length-tension curve of emphysematous animals was displaced toward the left; maximal tetanic tension was similar in all groups, while optimal length (Lo), defined as the length at which maximal twitch tension occurred, was significantly shorter in both emphysematous groups. The Lo was negatively correlated with the FRC. Exercise tended to increase the in vitro endurance of the diaphragm bundles in control animals only. Diaphragms from both emphysematous groups, however, did show the greatest resistance to fatigue. It is concluded that 1) daily running for 1 h does not influence the diaphragmatic contractile properties in the hamster, but fatigue was reduced; 2) the load of chronic emphysema decreased the hamster's diaphragm fatiguability; and 3) the diaphragms of emphysematous hamsters chronically adapt by decreasing diaphragmatic length in proportion to the degree of hyperinflation and thus probably continue to operate at an Lo.

Transdiaphragmatic pressure (Pdi) was measured at functional residual capacity (FRC) in four normal seated subjects during supramaximal, supraclavicular transcutaneous stimulation of one phrenic nerve (10, 20, 50, and 100 Hz--0.1 ms duration) before and after diaphragmatic fatigue, produced by breathing through a high alinear inspiratory resistance. Constancy of chest wall configuration was achieved by placing a cast around the abdomen and the lower one-fourth of the rib cage. Pdi increased with frequency of stimulation, so that at 10, 20, and 50 Hz, the Pdi generated was 32 +/- 4 (SE), 70 +/- 3, and 98 +/- 2% of Pdi at 100 Hz, respectively. After diaphragmatic fatigue, Pdi was less than control at all frequencies of stimulation. Recovery for high stimulation frequencies was complete at 10 min, but at low stimulation frequencies recovery was slow: after 30 min of recovery, Pdi at 20 Hz was 31 +/- 7% of the control value. It is concluded that diaphragmatic fatigue can be detected in man by transcutaneous stimulation of the phrenic nerve and that diaphragmatic strength after fatigue recovers faster at high than at low frequencies of stimulation. Furthermore, it is suggested that this long-lasting element of fatigue might occur in patients with chronic obstructive lung disease, predisposing them to respiratory failure.

To elucidate the role of serotonin in the maintenance of normal breathing and upper airway (UA) patency in obesity, we studied the effects of systemic administration of ritanserin, a serotonin (5-HT) 2A and 2C receptor antagonist, on ventilation (V E) during room air breathing and during hypoxic (10% O2) and hypercapnic (4% CO2) ventilatory challenges in awake young (6-8 wk) and older (7-8 mo) obese and lean Zucker (Z) rats. Older obese Z rats adopted a more rapid shallow breathing pattern compared with older lean rats. The administration of ritanserin (1 mg/kg intraperitoneally) to older obese rats resulted in a reduction in V E (439 +/- 35 [SD] to 386 +/- 41 ml/kg/min, p < 0.01), a decrease in respiratory rate, a prolongation of inspiratory time, and an increase in V O2 (16.4 +/- 1.7 to 18.2 +/- 1.9 ml/kg(0.75)/min, p < 0.05) during room air breathing. By comparison, it had little effect on ventilation in young lean and obese Z or older lean Z rats. Ritanserin also had no effect on ventilatory responses to either hypoxia or hypercapnia in young or older lean and obese Z rats. The collapsibility of the isolated UA was examined in older Z rats. The pharyngeal critical pressure (Pcrit) of older obese rats was significantly greater than that of lean rats (p < 0.05), indicating that obese rats have more collapsible UA than lean rats. The administration of ritanserin significantly increased Pcrit in older obese rats (-1.6 +/- 0.3 to -0.8 +/- 0.2 cm H2O, p < 0.01) and in lean rats (-3.1 +/- 1.0 to -2.4 +/- 0.6 cm H2O, p < 0.05). We suggest that the 5-HT(2A/2C) receptor subtype plays an important role in the maintenance of UA stability and normal breathing in obesity, and we speculate that older obese Z rats may have augmented serotonergic control of UA dilator muscles as a mechanism to prevent pharyngeal collapse.

The diaphragm is the primary muscle of inspiration, and as such uncompromised function is essential to support the ventilatory and gas exchange demands associated with physical activity. The normal healthy diaphragm may fatigue during intense exercise, and diaphragm function is compromised with aging and obesity. However, more insidiously, respiratory diseases such as emphysema mechanically disadvantage the diaphragm, sometimes leading to muscle failure and death. Based on metabolic considerations, recent evidence suggests that specific regions of the diaphragm may be or may become more susceptible to failure than others. This paper reviews the regional differences in mechanical and metabolic activity within the diaphragm and how such heterogeneities might influence diaphragm function in health and disease. Our objective is to address five principal areas: 1) Regional diaphragm structure and mechanics (GAF). 2) Regional differences in blood flow within the diaphragm (WLS). 3) Structural and functional interrelationships within the diaphragm microcirculation (DCP). 4) Nitric oxide and its vasoactive and contractile influences within the diaphragm (MBR). 5) Metabolic and contractile protein plasticity in the diaphragm (SKP). These topics have been incorporated into three discrete sections: Functional Anatomy and Morphology, Physiology, and Plasticity in Health and Disease. Where pertinent, limitations in our understanding of diaphragm function are addressed along with potential avenues for future research.

Covid‐19 disrupted the in‐person teaching format of anatomy. To study changes in gross anatomy education that occurred August‐December, 2020 compared to before the pandemic, an online survey was distributed to anatomy educators. The 191 responses received were analyzed in total and by academic program, geographic region, and institution type. Cadaver use decreased overall (before: 74.1 ± 34.1%, during: 50.3 ± 43.0%, P < 0.0001), as well as across allopathic and osteopathic medicine, therapy, undergraduate, and veterinary programs ( P < 0.05), but remained unchanged for other programs ( P > 0.05). Cadaver use decreased internationally and in the US ( P < 0.0001), at public and private ( P < 0.0001) institutions, and among allopathic medical programs in Northeastern, Central, and Southern ( P < 0.05), but not Western, US geographical regions. Laboratories during Covid‐19 were delivered through synchronous (59%), asynchronous (4%), or mixed (37%) formats ( P < 0.0001) and utilized digital resources (47%), dissection (32%), and/or prosection (21%) ( P < 0.0001). The practical laboratory examination persisted during Covid‐19 ( P = 0.419); however, the setting and materials shifted to computer‐based ( P < 0.0001) and image‐based ( P < 0.0001), respectively. In‐person lecture decreased during Covid‐19 (before: 88%, during: 24%, P = 0.003). When anatomy digital resources were categorized, dissection media, interactive software, and open‐access content increased (P ≤ 0.008), with specific increases in BlueLink, Acland’s Videos, and Complete Anatomy ( P < 0.05). This study provided evidence of how gross anatomy educators continued to adapt their courses past the early stages of the pandemic.

We investigated whether the shift in the diaphragmatic length-tension curve of emphysematous animals was due to changes in either sarcomere number or sarcomere length. In vitro length-tension characteristics of the diaphragm were evaluated in control and emphysematous hamsters. Emphysema was induced by a single endotracheal instillation of elastase. Functional residual capacity, measured by means of a plethysmograph, was about twice that measured in emphysematous animals compared with control animals. Small diaphragmatic bundles were isolated and evaluated for their length-tension characteristics. The length-tension curve of diaphragms from emphysematous animals was displaced toward the left. Maximal tetanic tensions were similar in both groups, whereas optimal bundle length was significantly decreased in the emphysematous animals. Sarcomere number and sarcomere length at optimal length were then calculated for the diaphragmatic bundles. The bundles from emphysematous animals were found to have a significantly reduced number of sarcomeres, as well as a significantly decreased sarcomere length at optimal compared with control values. The total number of sarcomeres were also found to be significantly negatively correlated with the animal's functional residual capacity. From these results, we conclude that the decrease in diaphragmatic length, seen with hyperinflation, is due mainly to a loss of sarcomeres and possibly to a small decrease in sarcomere length measured at optimal bundle length.

To have some insight into the functional coupling between the parasternal intercostals (PS) and the diaphragm (DPM), we have examined the isometric contractile properties of bundles from canine PS and DPM muscles. Bundles of external (EXT) and internal (INT) interosseous intercostals were studied for comparison. In addition we have related sonometrically measured length of the intercostals in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We found that 1) intercostal twitch speed is significantly faster than DPM, thus displacing their relative force-frequency curve to the right of that of the DPM; 2) the ascending limb of the active length-tension curve of all intercostals lies below the DPM curve; i.e., at 85% Lo, PS force is 46% of maximal force (Po), whereas DPM force is still 87% Po; 3) for any given length change beyond Lo, all intercostals generate greater passive tension than the DPM; 4) Po is greater for the intercostals than the DPM; and 5) at supine FRC, both EXT and INT in dogs are nearly operating at Lo, whereas the PS are operating at a length greater than Lo. We conclude that 1) PS produce less force than DPM during breathing efforts involving low- (10-20 Hz) stimulation frequencies, but they generate more force than DPM when high- (greater than 50 Hz) stimulation frequencies are required; and 2) the pressure-generating ability of the PS is better preserved than that of the DPM with increases in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

We hypothesized that adaptations of the rabbit diaphragm (Dia) after unilateral denervation (DNV) result from removal of a neural influence rather than from passive stress. Length changes of midcostal and sternal Dia regions were measured before and after DNV by using sonomicrometry. Midcostal fibers passively lengthened after DNV, whereas sternal fibers shortened. In both regions, these length changes were associated with minimal stress, as estimated from passive force-length relationships. Morphological and contractile adaptions of midcostal and sternal Dia regions were examined after 1 and 4 wk of DNV. In both Dia regions, type I fibers progressively hypertrophied, whereas type IIb fibers atrophied. After DNV, changes in isometric contraction were similar in both Dia regions. Twitch contraction and half-relaxation times increased, force-frequency relationships shifted leftward, and maximum tetanic force decreased. We conclude that passive length changes and mechanical stress are not the main determinants of the morphological and contractile adaptations of the Dia after unilateral DNV but that these adaptations result from DNV itself.