SARS-CoV2 infection: functional and morphological cardiopulmonary changes in elite handball players.

There is increasing evidence of cardiac involvement post-SARS-CoV-2 infections in symptomatic as well as in oligo- and asymptomatic athletes. This study aimed to characterize the possible early effects of SARS-CoV-2 infections on myocardial morphology and cardiopulmonary function in athletes. Eight male elite handball players (27 ± 3.5 y) with past SARS-CoV-2 infection were compared with four uninfected teammates (22 ± 2.6 y). Infected athletes were examined 19 ± 7 days after the first positive PCR test. Echocardiographic assessment of the global longitudinal strain under resting conditions was not significantly changed (- 17.7% vs. - 18.1%). However, magnetic resonance imaging showed minor signs of acute inflammation/oedema in all infected athletes (T2-mapping: + 4.1 ms, p = 0.034) without reaching the Lake-Louis criteria. Spiroergometric analysis showed a significant reduction in VO2max (- 292 ml/min, - 7.0%), oxygen pulse (- 2.4 ml/beat, - 10.4%), and respiratory minute volume (VE) (- 18.9 l/min, - 13.8%) in athletes with a history of SARS-CoV2 infection (p < 0.05, respectively). The parameters were unchanged in the uninfected teammates. SARS-CoV2 infection caused impairment of cardiopulmonary performance during physical effort in elite athletes. It seems reasonable to screen athletes after SARS-CoV2 infection with spiroergometry to identify performance limitations and to guide the return to competition.

The microvascular effects of photodynamic therapy: evidence for a possible role of cyclooxygenase products.

Photodynamic therapy (PDT) of malignant tumours may involve the interruption of tumor and peritumor microcirculation. We have studied the effect of light activation of the photosensitizing drug dihematoporphyrin ether (DHE) on rat subcutaneous arterioles and the modulation of these effects by cyclooxygenase inhibitors indomethacin and acetyl salicylic acid (ASA). Animals received DHE 48 h prior to light activation and additionally either indomethacin, ASA or saline 3 h prior to treatment. Light activation (630 nm, 60 J/cm2) resulted in a significant reduction to 62 +/- 2% SEM of initial blood flow. This effect was inhibited by ASA (98 +/- 8% SEM) and indomethacin (87 +/- 8% SEM). Results from the administration of various doses of both compounds indicate that this inhibition is dose related. The data presented here show that PDT causes a significant reduction in blood flow in normal arterioles and that this effect was inhibited by ASA and indomethacin indicating that prostaglandins or thromboxane A2 may play an important role in the microvascular response to PDT.

The effect of photodynamic therapy on the microcirculation.

Photodynamic therapy (PDT) is a new form of cancer therapy involving tumor localization by photosensitizing drugs such as dihematoporphyrin ether (DHE). Light irradiation of drug-sensitized tissue results in photoactivation of DHE and tumor necrosis. The mechanism of action is incompletely understood but involves the generation of singlet oxygen which produces cytotoxic effects on tissues containing the compound. In addition, microcirculatory aberrations have been described during PDT. We have studied the acute effects of PDT on the microcirculation using in vivo television microscopy of the rat cremaster. This has enabled us to observe the effects of PDT on both paired and unpaired arterioles and venules using two different wavelengths of activating light (blue, 450-490 nm, and green, 530-560 nm). For both wavelengths of activating light, significant reduction in blood flow of all vessels was seen during PDT. This, in combination with the formation and embolization of platelet thrombi, resulted in stasis of blood flow in 80% of arterioles and 90% of venules. Observation for 2 hr after the completion of photoactivation revealed reperfusion in 20% of the arterioles but none of the venules. Blood flow was reduced by a combination of vasoconstriction and platelet thrombus formation. Reducing the total activating energy from 120J/cm2 to 24J/cm2 significantly reduced the response in venules and the incidence of stasis in both arterioles and venules. We conclude that the photoactivation of DHE results in significant vasoconstriction and thrombosis of normal vessels and that if these effects are seen at later times after DHE administration and in tumor neovasculature they may contribute to the mechanism by which PDT results in tumor necrosis.

Protein leak from normal vasculature due to human malignant ascites.

Malignant ascites is an accumulation of protein rich fluid (a filtrate of whole blood) in the peritoneal cavity of patients with abdominal malignancies. The normal peritoneal microvasculature of the cremaster muscle of rats, with the nerve and blood supply intact, was visualized before and after exposure of the tissue to human malignant ascites fluid and to human plasma. In vivo fluorescent microscopy was used to quantitate leakage of fluorescent-tagged albumin. Exposure of the abluminal side of the vasculature to malignant ascitic fluid and plasma causes significant protein leakage from the small veins to the interstitial space. This suggests that the continued production of malignant ascites may be caused by a positive feedback system, which is related to factors present in a normal plasma filtrate. These factors can induce leakage of protein by an effect on the abluminal side of the normal peritoneal microvasculature.

Human malignant ascites and histamine-induced protein leakage from the normal microcirculation.

The accumulation of malignant ascites is a significant cause of morbidity and mortality in patients with intraabdominal malignancies. However, the cause of malignant ascites is unknown. In this study, we used the rat cremaster muscle preparation to determine if and how malignant ascites could produce protein leakage from normal blood vessels which would lead to fluid accumulation in the peritoneal cavity. The rat cremaster muscle, with nerves and blood vessels to the animal intact, was prepared for microscopic observations of the microcirculation. Serum albumin was tagged to fluorescein isothiocyanate and injected into the rat. Fluorescent microscopy was used to quantitate leakage of the tagged albumin into the interstitial tissue. Malignant ascites was collected from a patient with metastatic breast cancer. The ascites fluid was placed on the cremaster muscle and it induced protein leakage from the normal blood vessels of this tissue. Protein leakage was partially blocked by diphenhydramine (10(-4) M) and by mast cell depletion with compound 48/80. There was a high level of C3a in the malignant ascites solution but C3a did not increase during the exposure period. These data suggest that activated complement in malignant ascites may release histamine from mast cells to cause protein leakage of the normal vasculature. The movement of protein into the peritoneal cavity would be followed by water, thus increasing the volume of the ascites and exacerbating the clinical condition.