A low-cost, highly functional, emergency use ventilator for the COVID-19 crisis.

Respiratory failure complicates most critically ill patients with COVID-19 and is characterized by heterogeneous pulmonary parenchymal involvement, profound hypoxemia and pulmonary vascular injury. The high incidence of COVID-19 related respiratory failure has exposed critical shortages in the supply of mechanical ventilators, and providers with the necessary skills to treat. Traditional mass-produced ventilators rely on an internal compressor and mixer to moderate and control the gas mixture delivered to a patient. However, the current emergency has energized the pursuit of alternative designs, enabling greater flexibility in supply chain, manufacturing, storage, and maintenance considerations. To achieve this, we hypothesized that using the medical gasses and flow interruption strategy would allow for a high performance, low cost, functional ventilator. A low-cost ventilator designed and built-in accordance with the Emergency Use guidance from the US Food and Drug Administration (FDA) is presented wherein pressurized medical grade gases enter the ventilator and time limited flow interruption determines the ventilator rate and tidal volume. This simple strategy obviates the need for many components needed in traditional ventilators, thereby dramatically shortening the time from storage to clinical deployment, increasing reliability, while still providing life-saving ventilatory support. The overall design philosophy and its applicability in this new crisis is described, followed by both bench top and animal testing results used to confirm the precision, safety and reliability of this low cost and novel approach to mechanical ventilation. The ventilator meets and exceeds the critical requirements included in the FDA emergency use guidelines. The ventilator has received emergency use authorization from the FDA.

Ultrasound energy improves myocardial perfusion in the presence of coronary occlusion.

OBJECTIVES: We evaluated whether ultrasound improves myocardial tissue perfusion in 14 animals with coronary artery occlusion. BACKGROUND: A recent study demonstrated that low-frequency ultrasound improves tissue perfusion in the rabbit ischemic limb, but there are no data on ultrasound enhancement of myocardial perfusion. METHODS: Fourteen animals (9 dogs, 5 pigs) underwent thoracotomy and occlusion of a diagonal branch of the left anterior descending coronary artery. Myocardial tissue perfusion units (TPUs) and pH were measured before coronary occlusion, after occlusion, and after direct exposure of the ischemic myocardium in the presence of fixed occlusion to low-frequency ultrasound (27 kHz). RESULTS: The TPU decreased from 100.9 +/- 13 at baseline to 71.1 +/- 13 (p < 0.01) after 60 min occlusion but rose by 19.7% to 85.1 +/- 8 (p < 0.01) after ultrasound exposure for 60 min. After 60-min coronary occlusion, myocardial pH fell from 7.43 +/- 14 to 7.05 +/- 0.15 (p < 0.01) but then improved to normal (7.46 +/- 0.32) after ultrasound for 60 min. Administration of L-Nomega-nitro-arginine methyl esther (L-NAME), an inhibitor of nitric oxide synthase, before ultrasound exposure, blocked improvement in myocardial tissue perfusion and pH by ultrasound. Quantitative histomorphology showed a significant increase in the capillary area of myocardium exposed to ultrasound versus non-exposed myocardium (16.2 +/- 7.9 vs. 8.2 +/- 2.1, p < 0.02). CONCLUSIONS: Low-frequency, low-intensity ultrasound improves myocardial tissue perfusion and pH in the presence of a fixed coronary artery occlusion.

Coronary vasodilation by noninvasive transcutaneous ultrasound: an in vivo canine study.

OBJECTIVES: We evaluated the coronary vasodilatory effects of transcutaneous low-frequency (27-kHz) ultrasound (USD). BACKGROUND: Ultrasound has been shown to affect vascular function. METHODS: Ultrasound energy was administered transcutaneously to 12 dogs. Coronary arterial dimensions were assessed using intravascular coronary ultrasound (IVUS) and quantitative coronary angiography (QCA). RESULTS: The IVUS mid-left anterior descending (LAD) luminal area was 6.77 +/- 1.27 mm(2) at baseline. After 30 s of ultrasound, this area increased by 9% (7.40 +/- 1.44 mm(2), p < 0.05), after 3 min by 19% (8.05 +/- 1.72 mm(2), p < 0.05) and after 5 min increased by 21% (8.16 +/- 1.29 mm(2), p < 0.05). The mean coronary diameter (2.69 +/- 0.33 mm) at baseline (QCA of three segments of LAD and three segments of left circumflex coronary artery) increased by 19.3% (3.21 +/- 0.28 mm) after 5 min of USD exposure. After a 90-min observation period there was a return to baseline values (p = NS). Intracoronary nitroglycerin (NTG) administered to five dogs revealed a similar magnitude of vasodilation as USD. CONCLUSIONS: Noninvasive, transthoracic low-frequency USD energy results in coronary artery vasodilation within seconds of exposure. The vasodilation is reversible and is similar in magnitude to that induced by NTG. Further evaluation is needed to assess its potential applications in humans.

Noninvasive transcutaneous ultrasound augments thrombolysis in the left circumflex coronary artery--an in vivo canine study.

BACKGROUND: Ultrasound has the potential to augment chemical thrombolysis. METHODS AND RESULTS: Thrombotic occlusions in the left circumflex artery (LCx) were induced in 27 dogs. Sixty minutes later, tissue-type plasminogen activator (t-PA) was given intravenously over 90 min. Thrombotic occlusions (n = 20) were treated with concomitant transcutaneous low frequency (27 kHz), continuous wave (CW) (n = 10) or pulsed wave (PW) (n = 10) ultrasound. Tissue-type plasminogen activator plus ultrasound (n = 20) vs. tissue-type plasminogen activator alone (n=7) resulted in more frequent Thrombolysis in Myocardial Infarction (TIMI) 3 flow (90% vs. 43%, P = 0.024) and less reocclusion (11% vs. 67%, P = 0.080). At 60 min, median TIMI grade flow for tissue-type plasminogen activator alone was 2 (mean: 1.43 +/- 1.40) compared to 3 (mean: 2.70 +/- 0.95) for tissue-type plasminogen activator plus continuous as well as pulsed wave ultrasound (P = 0.035). Continuous wave and pulsed wave ultrasound were equally effective in augmenting thrombolysis. Histologically, no ultrasound-mediated injury to the myocardium or coronary arteries occurred. CONCLUSION: Both transcutaneous low frequency continuous wave ultrasound and pulsed wave ultrasound enhance tissue-type plasminogen activator-mediated thrombolysis of the posterior circulation with higher TIMI 3 flow rates and less reocclusion than with tissue-type plasminogen activator alone. In addition, at the energy levels used, low frequency ultrasound appears safe.